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Background Resveratrol, a bioactive phytoconstituent, is used to treat chronic respiratory diseases. However, its clinical application was hampered due to its poor bioavailability. In the present study, controlled release of resveratrol loaded nanocochleate-based dry powder inhaler was investigated to improve its biopharmaceutical properties for pulmonary drug delivery. The in vivo toxicity study was performed in the healthy male albino Wistar rats by intracheal administration. Results Resveratrol loaded nanocochleate-based dry powder inhaler was prepared by lyophilizing the resveratrol loaded dimyristoylphosphatidylcholine sodium and calcium ion-based nanocochleates using mannitol as cryoprotectant. Resveratrol loaded nanocochleates showed a particle size and encapsulation efficiency of 329.18 ± 9.43 nm and 76.35 ± 3.65%, respectively. Resveratrol loaded nanocochleate-based dry powder exhibited a particle size of 102.21 ± 9.83 μm and satisfactory flowability with initial burst release followed by extended release up to 96 h. The in vitro drug deposition pattern using multistage cascade impactor showed 1.28-fold improvement in fine particle dose, and the in vivo toxicity potential by histopathological study in albino rats revealed safety of formulation. Conclusions Resveratrol loaded nanocochleate-based dry powder inhaler could serve as an efficient delivery system for the treatment of chronic respiratory diseases. Graphical abstract

Objective: To study the Therapeutic drug monitoring and pharmacokinetics of marketed antibiotics formulation by developing a sensitive and specific Bioanalytical Chromatographic method. Methods: In the present study, we developed a rapid, sensitive and selective chromatographic method for simultaneous estimation of Cefoperazone (CEF) And Sulbactam (SAL) in male Wistar rat plasma. A novel liquid phase extraction method has adopted the preparation of plasma sample preparation. The CEF and SAL were eluted on a peerless Basic C18 (25 cm; 4.6 mm x 5 µm) column maintained at controlled environmental conditions. The gradient mobile phase comprised of 10 mmol ammonium acetate and acetonitrile. A UV detector was set at 250 nm and retention times for CEF and SAL were approximately 5.6 and 14.2 min, respectively. The proposed HPLC method was validated according to the US FDA guidelines with respect to the linearity, accuracy, precision, detection and quantitation limits, robustness and specificity. Results: Calibration curves of CEF and SAL were linear across the concentration range of 600-1000 and 6-10 µg/ml, with correlation coefficients (r2)>0.9977 and (r2)>0.9987, respectively. The limits of detection for CEF and SAL were 70.48 and 0.35 µg/ml, respectively. Additionally, CEF and SAL were stable in plasma for at least 24 h when stored at room temperature and 2-8 °C. Conclusion: The developed chromatographic method was effectively utilized to measure the plasma CEF and SAL concentrations in a pharmacokinetics study after intravenous injection to the healthy male Wistar rats.

The aim of the present investigation was to develop adapalene (ADP), a high lipophilicity and low solubility anti-acne drug-loaded niosomal topical gel formulation, in order to improve its therapeutic efficacy. ADP niosomes were prepared using Span 60 and cholesterol using a modified ethanol injection method. A design of experiments (DOE) study was conducted to optimize ADP loaded niosomes. The potential of ADP niosomes was investigated for in vitro release and ex vivo skin permeation studies. Additionally, ADP niosomes were loaded into the Carbopol 934 gel and studied for its skin irritation, skin deposition and ex vivo skin permeation potential. The developed ADP niosomes showed the mean particle size, zeta potential, and entrapment efficiency of 278 nm, −17.99 mV, and 86%, respectively. The optimized ADP niosomes showed controlled drug release up to 12 h. Nevertheless, the niosomal gel displayed controlled drug release up to 24 h with a reduction in skin irritation in Wistar rats. An in vivo skin deposition study showed 2.5-fold higher ADP retention in the stratum corneum layer as compared to the commercial ADP formulation. The ADP niosomal gel would be a safe and valuable alternative to the conventional delivery systems for the treatment of acne.

Objective: To study fixed-dose combinations (FDC) of antibacterial and antiprotozoal products (ofloxacin and azoles), prescribed for the treatment of diarrhea. Methods: Rationality of these FDC products was verified by assessing parameters such as drug content and release by assay and dissolution tests, respectively mentioned in the Indian Pharmacopoeia (IP). Amount of drug solubilized and permeated as per the Biopharmaceutics Classification System (BCS) was determined. Ex vivo permeation study was performed on the gut of goat using the everted gut sac technique. Antimicrobial efficacy in terms of minimum inhibitory concentration (MIC) was assessed using agar well diffusion method against Shigella boydii, the causative agent for diarrhea. Comparative studies were performed on an individual as well as combination doses of antibacterial and antiprotozoal products for the synergistic effects to assess the rationale of these FDC. Results: The BCS solubility of ciprofloxacin (CPX), norfloxacin (NFX) and tinidazole (TNZ) was high in acidic medium (pH 1-5) and decreased at pH above 5. The assay studies showed that the individual drug contents of FDC were within the IP limits. In vitro dissolution results for both, individual drugs and their combination illustrated 99 % drug release within 30 min in 0.01N HCl. Ex vivo permeation of TNZ was higher than CPX and NFX in individual drugs. No significant change in the permeation rate was observed for individual drugs and their FDC. CPX and NFX exhibited more antimicrobial activity in terms of inhibitory zones than their FDC with antiprotozoal TNZ, above 2.5 µg/ml MIC. The pharmaceutical, biopharmaceutical and antimicrobial evaluation study showed the similarity of FDC with the individual drugs. Conclusion: The study showed no significant data to justify the therapeutic advantage of FDC over individual drugs.

This study aimed at carrying out a preformulation investigation of nanocochleates (NCs) and develop andrographolide-loaded nanocochleates. Preformulation study comprised of exploring the effect of trivalent and divalent ions on transition temperature (TT) of lipid (DMPG-Na), on particle size (PS), entrapment efficacy (EE), zeta potential (ZP) of NCs, and effect of NCs on change in lipid solubility post-NC formation. Further, the andrographolide-loaded nanocochleates made with CaCl2 (ANDNCs) were characterized for ZP, PS, EE, X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), transition electron microscopy (TEM), in vitro release studies, in vitro anticancer potential on the cell line of human breast cancer (MCF-7), in vivo oral pharmacokinetic studies, and tissue distribution in female Wistar rats. Nanocochleates developed with CaCl2 had a significant reduction in PS (1.78-fold) and ZP (1.38-fold), and elevation of EE (1.17-fold) as compared to AlCl3 developed NCs. Trivalent ions demonstrated elevation of TT as compared to divalent ions. Spiral-shaped ANDNCs demonstrated ZP, PS, and EE of − 121.46 ± 15.12 mV, 360 ± 47 nm, and 68.12 ± 3.81% respectively. In vitro release study of ANDNCs showed a strong pH-dependent release profile due to hydrogen bonding between NCs and andrographolide (AND). Formulated ANDNCs demonstrated 26.99-fold decrease in IC50 value as compared to free AND. Additionally, the oral bioavailability of AND from ANDNCs improved by 1.81-fold as compared to free AND. Furthermore, ANDNCs showed minimum accumulation within the vital organs such as liver, kidney, and spleen. Briefly, the preformulation study laid a platform for better understanding the NCs and its components. Further, developed ANDNCs revealed superior physiochemical properties to be used as an alternative for a clinical setting.

The present investigation aimed to develop curcumin loaded turmeric oil microemulsion for brain targeting. An effort has been made to investigate the role of functional components in developing brain targeted formulation which could enhance the bioavailability and uptake of drug in the brain upon oral administration. Preliminary studies like solubility study, emulsification study and construction of the pseudo ternary phase diagram were performed for screening components. The formulation was optimized by using extreme vertices mixture design. The optimized formulation was characterized for appearance, stability to centrifugation, dilution potential, globule size, zeta potential and drug content. Furthermore, ex-vivo permeation in chicken gut sac non everted technique and pharmacokinetic study in adult zebra fishes were carried out. The optimized formulation was found to clear, yellow-colored with the absence of phase separation and precipitation denoted the stability of formulation to centrifugation and dilution. The mean globule size, polydispersity index, zeta potential and drug content was observed as 29.13± 0.12 nm, 0.23 ± 0.01,-12.33 ± 1.37 mV and 99.10±3.91 %, respectively. Ex vivo permeation study revealed 2.41 fold enhancement in the steady-state flux when compared to curcumin solution. Furthermore, optimized formulation showed shorter Tmax (5 min) and higher AUC(0-∞) (7.93 μg/brain*min) compared to the curcumin solution which showed similar Tmax and AUC(0-∞) of 2.78 μg/brain*min after oral administration to zebra fishes revealing 3.97 fold enhancement. The results revealed enhanced ex vivo oral absorption and enhanced in vivo brain pharmacokinetics of curcumin via functional microemulsion in the zebra fish model.

The objective of the present study is to understand the effects of lactose fines, a USP modified induction port (IP) and USP modified glass sampling apparatus (DDU apparatus) on the aerodynamic behavior of a fluticasone propionate (FP) dry powder inhaler (DPI). Lactose carriers containing 0 to 25% lactose fines were assessed for various physicochemical properties. Also, formulated FP DPIs were analyzed in terms of aerodynamic behavior using a multistage cascade assembly and DDU apparatus equipped with Revolizer® at a flow rate of 60 L min−1. The physicochemical characterization of lactose carriers showed that there were remarkable differences in particle size distribution, surface area and surface roughness. The formulated FP DPIs exhibited acceptable percentage content uniformity (>96%). A cascade impactor equipped with the USP modified IP showed significant differences in recovered and emitted doses compared to the USP IP. Additionally, in comparison to the USP IP, the USP modified IP showed a lower amount of drug deposition within the IP, irrespective of the lactose fines concentration. Besides, a formulated FP DPI showed a higher (>95%) mean delivered dose using the modified DDU apparatus at a flow rate of 60 L min−1. Briefly, not only the formulation properties and inhalation device but also the IP geometry had significant impacts on the in vitro analysis. The present investigation is the first detailed account of FP aerosolization performance using USP modified IP and DDU apparatus. Therefore, these findings may be of high importance for both academics and industrial researchers.

Dendrimers and dendrimer-based delivery systems are potential biomedicines in the rapidly growing field of nanomedicine. At present, dendrimers are drawing attention in the scientific domain due to their unique structural features, physiological properties and biological attributes. These multifunctional nanomaterials provide unique platforms for targeting, imaging, diagnostics and theranostics. The rationale of this article is to offer insight into the pulmonary delivery of these multifunctional nanomaterials. This review examines reports on inhaled dendrimers which have been published in the last few years. The article begins by describing the relevant background knowledge of dendrimers, dendrimer synthesis schemes and their potential advantages as nanomaterials. It progresses to the pulmonary applications of dendrimers, with special emphasis on pressurized metered-dose inhalers (pMDIs), soft mist inhalers (SMI), nebulizers and dry powder inhalers (DPI). Additionally, this review article contains a dedicated section discussing the biocompatibility challenges and clinical outcomes of dendrimer-based nanotherapeutics. In summary, this review is the first comprehensive account of inhaled dendrimers to appear in recent years.

Fisetin (FS), 2-(3,4 dihydroxyphenyl)-3,7-dihydroxychromen-4-one), a bioactive natural hydrophobic flavonol, has numerous therapeutic properties. However, its efficacy as a potential phytochemical has been limited owing to poor aqueous solubility and consecutively bioavailability. In the present study, we report the co-crystal synthesis of FS with caffeine (CA, 1,3,7-trimethylpurine-2,6-dione) and a nicotinamide (NC, pyridine-3-carboxamide) co-former using cooling crystallization technology to augment the biopharmaceutical properties of FS. A methanolic solution containing FS and co-formers was subjected to cooling crystallization to acquire the FS co-crystals. The developed co-crystals were analyzed using differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffractometry, scanning electron microscopy, saturation solubility and intrinsic dissolution studies. The oral bioavailability of the co-crystals was studied using healthy Wister male rats. In addition, the anti-inflammatory potential of the co-crystals was studied using a carrageenan-induced rat paw edema model. Cooling crystallization caused development of golden yellow colored cylindrical FS–CA and rectangular FS–NC co-crystals, as verified by thermal and diffractometry analysis which exhibited more than a two-fold enrichment in the solubility of FS. The FS–CA co-crystal displayed a marked three-fold improvement in the oral bioavailability of FS and retained the anti-inflammatory potential of FS in the pharmacodynamic study. The investigation showed the utility of cooling crystallization technology to augment the biopharmaceutical properties of bioactive FS and could be explored for clinically important lipophilic phytochemicals to improve their pharmaceutical properties.

Methotrexate (MTX) plays important treatment modalities for several paediatric cancers. Several automated binding assays and chromatographic methods was developed for estimating Methotrexate levels...

One of the characteristics of amphiphilic drug which may be a disadvantage is the phase separation or clouding phenomenon on heating which depends upon the nature, structure and concentration of th...

Methotrexate (MTX), a potent anticancer drug, shows low oral bioavailability due to its low aqueous solubility and permeability. Moreover, its multidrug resistance (MDR) in cancer and toxic effects restricts its clinical applications. The aim of the study was to prepare novel MTX-loaded Poloxamer 407 and Gelucire®44/14 (GL44) mixed micelles (MTX-PGMM) to improve its oral bioavailability and cytotoxicity and to reduce its systemic toxicity. MTX-PGMM was prepared by dialysis method, compared with blank or MTX-free blank mixed micelles (BMM) and aqueous dispersion of MTX (MTX-AD) with respect to morphology, size, zeta potential, entrapment efficiency, in vitro release, and in vitro cytotoxicity, bioavailability, and toxicity study in rats. The developed MTX-PGMM exhibited small particle size, good encapsulation efficiency, and good stability in media simulating the physiological conditions of the gastrointestinal tract. The MTX-PGMM micelles demonstrated sustained release, enhanced (6.5-fold) oral bioavailability, slow plasma elimination, and long circulation of MTX. Biocompatibility was also established as there were no signs of tissue toxicity. Moreover, MTX-PGMM produced higher in vitro cytotoxicity (GI50 of 1.44 ± 0.33 μg/mL) than free MTX (GI50 13.71 ± 0.99 μg/mL) in human breast cancer MCF-7 cells. Poloxamer 407 and Gelucire®44/14 (GL44) mixed micelles are promising carriers for oral delivery of MTX and can be utilized for other Biopharmaceutical Classification System class IV anticancer drugs having poor oral bioavailability and multidrug resistance in cancer.

A new family of biofunctionalized chitosan decorated nanocochleates-mediated drug delivery system was developed that involves uniquely combining nanocochleates with anticancer drug for controlled drug release, targeted delivery, improved bioavailability with reduced toxicity. This system was developed by loading of doxorubicin (DOX) to nanocochleates (DOX-NC) through conversion of negatively charged dimyristoylphosphatidylcholine (DMPC) phospholipid and cholesterol-bearing vesicles on addition of calcium ions, followed by encapsulation DOX-NC with folic acid conjugated chitosan (FA-CHI-DOX-NC). The release of DOX indicated strong pH dependence and implies hydrogen-bonding interaction between nanocochleates and DOX. Formulated FA-CHI-DOX-NC demonstrated higher in-vitro anticancer activity in folate overexpressed human breast cancer MCF-7 cells. The targeting effect for the FA-CHI-DOX-NC was also demonstrated. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 9.1 µg/ml for DOX while it was decreased by 31.68% for the DOX-NC (6.2 µg/ml). Furthermore, the GI50 value of FA-CHI-DOX-NC was 4.4 µg/ml, i.e. a 51.64% decrease was observed as compared to DOX solution. Moreover, bioavailability of DOX from FA-CHI-DOX-NC increased by 4-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to DOX solution. The proposed strategy is advantageous in terms of targeted drug delivery and has high potential to address the current challenges in drug delivery. Thus, the prepared new carrier offers a novel formulation that combines the unique properties of a biodegradable material, chitosan and nanocochleates for biomedical applications.

The natural flavonoid fisetin (FS) has shown anticancer properties but its in-vivo administration remains challenging due to its poor aqueous solubility. The aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA) conjugated micelles (FS-PF-FA) by the way of increasing solubility, bioavailability and active targetability of FS shall increase its therapeutic efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS-PF-FA micelles were prepared by thin-film hydration method and evaluated in comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 ± 6.1 nm), good encapsulation efficiency (82.50 ± 1.78%), zeta potential (-26.7 ± 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF micelles was increased by 6-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to free FS. Further, the FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed human breast cancer MCF-7 cells. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 14.3 ± 1.2 µg/ml for FS while it was greatly decreased to 9.8 ± 0.78 µg/ml, i.e. a 31.46% decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 ± 0.4 µg/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF. The results indicate that the FS-PF-FA micelles have the potential to be applied for targeting anticancer drug delivery.

Cholecalciferol, is a fat soluble vitamin D3 (Vit.D3), recognized in promoting bone health in children and adults and also it has other health benefits. Vit.D3 has suggested being dependent on bile salts for the formation of mixed micelles which is a pre requisite for its absorption. The efficiency of oral absorption of conventional Vit.D3 is approximately 50 %. Arachitol Nano™ is a commercially available nanoparticle based novel drug delivery system (NDDS) of Vit.D3. Data on the uptake of Vit.D3 from the NDDS (Arachitol Nano™) through the intestinal epithelium is not documented. The aim of the study was to investigate the absorption of a nanoparticle based NDDS of Vit.D3 (Arachitol Nano™) using everted rat intestinal sac technique. The results of the study suggested that Vit.D3 from Arachitol Nano™ showed a nonspecific absorption through various segments of rat small intestine, with high flux, permeability coefficient and percentage of absorption (79.21 ± 0.23, 76.55 ± 0.24 and 77.73 ± 0.24 % for duodenum, jejunum and ileum). The average absorption of Arachitol Nano™ was 77.83 ± 0.24 % through rat small intestine. The predicted human absorption may be more than 90 %. The study demonstrates that water soluble nanoparticle Vit.D3 (Arachitol Nano™) can substantially increase the oral absorption of the vitamin D3 and thus can be useful in the oral delivery of vitamin D3.

Polyurethanes (PUs) constitute an essential class of stimuli-responsive and biodegradable material, which has significantly contributed to the advancement of polymers utilization in the biomedical field. The bio-erodible PUs construct an active corridor for facilitating drug into tumor cells, which has significantly impacted the progression of nano-micellar delivery systems. The self-assembled colloidal PUs pose distinctive features such as enhancing the solubility of hydrophobic chemotherapeutics, rapid cellular uptake, triggered erosion and drug release, bio-stimulus sensitivity, improvement in the targeting and proficiency of bioactive. Cationic PUs can easily be condensed with genetic material to form polyplexes and have shown excellent transfection efficiency for potential gene therapy against various cancers. Their modifiable chemistry offers a tool to impart the desired multifunctionality such as biocompatibility, sensitivity to pH, redox, temperature, enzyme, etc. and ligand conjugation for active targeting. These diverse exceptional properties make them excellent nano-carrier for a variety of bioactive, including chemotherapeutic drugs, DNA, RNA, and diagnostic moieties to the target tissue or cells. The PUs based nano-devices have certainly uncovered the path to achieve ideal systems for controlled personalized therapy. The literature discussed in this review shed light on the research innovations carried out in the last ten years for the development of multifunctional PUs for triggered delivery of bioactive to treat various cancers.

In the present study, a lactose based dry powder inhaler (DPI) was formulated to probe the effect of three different US Pharmacopeia (USP) induction port (IP) on aerosolization performance DPIs. Additionally, the delivered dose uniformity (DDU) and drug-carrier detachment were studied using the USP modified glass sampling apparatus and force-displacement concept, respectively. Initially, median sized lactose carrier (InhaLac® 160) and a model drug fluticasone propionate (FP) were studied for numerous physicochemical properties. The homogenous drug-carrier blend was prepared using a low shear 3D shaker mixer. The InhaLac® 160 showed typical tomahawk-shaped particles with mean particle size (d50) and average surface roughness of 109.46 μm and 2.70 μm, respectively. Additionally, the laser Raman spectrometry demonstrated the uniform surface distribution of FP across the carrier surface. In the drug-carrier detachment study, FP DPI required >600 g-force to detach the 50% of the FP particles from lactose surface. During cascade analysis, all three USP IPs showed a remarkable variation in drug retention within the IP and pre-separator. The USP modified IP showed superior % fine particle fraction as compared to the USP IP. The difference in aerodynamic dispersion can be attributed to the variation in the design of the USP IPs. Moreover, developed FP DPI showed satisfactory DDU (>88%) when studied using the modified glass sampling apparatus. Briefly, the present study offers a detailed report on aerosolization performance of median sized lactose carrier-based DPIs using different USP IPs.

The present study aimed to probe influences exerted by extrinsic lactose fines on drug detachment and delivered dose uniformity (DDU) of fluticasone propionate (FP) dry powder inhaler (DPI). Extrinsic lactose fines (0–35%) containing lactose pre-blends were formulated using a low shear 3D shaker mixer and systematically analyzed for various physicochemical properties. Moreover, formulated FP DPIs were assessed for drug detachment by force distribution concept and the DDU using two different sampling devices i.e. the Dosage Unit Sampling Apparatus (DUSA) and USP modified glass sampling device (modified DUSA) coupled with Aerolizer® device at 60 L/min. The physicochemical assessment of control and pre-blend lactose samples displayed significant differences in particle size, surface roughness, degree of surface irregularity and powder flow properties. The formulated FP DPIs displayed monolayer-type FP distribution across the lactose particles in laser Raman spectroscopy with acceptable content uniformity (~100%). Drug detachment study using a modified centrifuge tube showed significant differences in drug detachment profile. The FP DPI formulated using 20% of lactose fines showed the lowest drug detachment force (349.45 gf) as compared to the other lactose samples. Moreover, the FP DPI formulated using 20% of lactose fines demonstrated acceptable mean delivered dose (107.76 and 110.62 μg) with the lowest coefficient of variation using DUSA and modified DUSA, respectively. The present study is the first comprehensive summary of delivered dose uniformity using two different USP sampling devices. Accordingly, these observations may be of high significance for both intuitional and industrial formulators.

The present investigation is to study the effect of two different induction ports (IP), i.e., USP IP and USP-modified IP equipped with andersen cascade impactor on in vitro aerodynamic performance along with the impact of USP-modified glass sampling apparatus on delivered dose uniformity of fluticasone propionate (FP) dry powder inhaler (DPI). FP DPI was fabricated by spray drying technique using engineered mannitol microparticles (EMP) with different force controlling agents, i.e., leucine and magnesium stearate. Additionally, commercially available two DPI inhaler devices namely Handihaler® and Breezhaler® were used to aerosolize the FP blends. Spherical smooth surface of EMP showed good powder flow properties and acceptable percentage content uniformity (> 95%). Amounts of FP deposited in cascade assembly using USP-modified IP with the Breezhaler® device was significantly higher (1.32-fold) as compared with the Handihaler® device. Moreover, USP-modified IP showed better deposition as compared with USP IP. Additionally, both inhaler devices showed a satisfactory delivered dose (> 105%) for FP using modified glass sampling apparatus at a flow rate of 60 L/min for 2 s. It was interesting to note that not only formulation properties but also IP geometry and device resistance have significant impact on DPI deposition pattern. This study is a first detailed account of aerodynamic performance of FP using USP-modified IP and USP-modified glass sampling apparatus. Thus, it can be of potential importance for both the academic and industry perspective.

The number of unit operations to be followed in the preparation of tablets was cumbersome and may introduce material as well as process-related critical parameters which may negatively affect the quality of final formulation. The hypothesis of the present research was to develop directly compressible, high-strength extended-release spherical agglomerates of talc containing indapamide by crystallo-co-agglomeration technique. Hydroxypropyl methylcellulose 15 cps and polyethylene glycol 6000 were used to impart the desired sphericity, strength, and deformability to agglomerates, respectively. Ethyl cellulose 10 cps was used to improve the strength of agglomerates and achieve extended release. Design of experiment (rotatable central composite design) was implemented for the elucidation of the effect of type and quantity of polymers on quality attributes of agglomerates. Prepared agglomerates were evaluated for morphological, micromeritic, mechanical, and drug release properties. A satisfactory yield (> 97%, wt/wt), better crushing strength, and low friability of agglomerates indicated good processing and handling characteristics. Compatibility and reduced crystallinity of indapamide in agglomerates were confirmed by spectroscopic and X-ray diffraction studies. Formation of the miniscular dosage form and hydrophobicity of talc were the key factors observed in controlling and extending the drug release (up to 6 h) from agglomerates. Hence, the developed crystallo-co-agglomeration technique could be successfully used for the preparation of directly compressible high-strength extended-release spherical agglomerates of indapamide.

The motive of study was to develop biotinylated chitosan (BI-CHI) decorated docetaxel (DTX) loaded nanocochleates (BI-CHI-DTX-NC) to achieve controlled drug release, improve bioavailability, targeted delivery and enhanced anticancer potency with the reduced systemic toxicity of DTX. The development involved the loading of DTX to nanocochleates (DTX-NC) through conversion of dimyristoylphosphatidylglycerol-sodium (DMPG-Na) and cholesterol bearing liposome on addition of calcium ions, followed by encapsulated DTX-NC with BI-CHI (BI-CHI-DTX- NC) and compared with DTX and DTX-NC. The release of DTX indicated strong pH dependence and implies strong hydrogen-bonding between nanocochleates and DTX. Formulated BI-CHI-DTX-NC demonstrated higher in-vitro anticancer activity in biotin over expressed human breast cancer MCF-7 cells. The targeting effect for the BI-CHI-DTX-NC was also demonstrated. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 1.8 μg/ml for free DTX while it was decreased by 33.34% for the DTX-NC (1.2 μg/ml). Furthermore, the GI50 value of BI-CHI-DTX-NC was 0.2 μg/ml, i.e. an 88.89% decrease was observed as compared to DTX solution. Moreover, bioavailability of DTX from BI-CHI-DTX-NC was increased by 10-folds with longer circulation time and slower plasma elimination with low tissue distribution as compared to DTX solution. The results indicate that the BI-CHI-DTX- NC has the potential to be applied for targeting anticancer drug delivery.

Resveratrol (RES) is a natural lipophilic, useful anticancer molecule. However, due to its low aqueous solubility and extensive metabolism in the intestine and liver, RES shows poor oral bioavailability. The aim of this study was to develop a novel method to deliver RES, using piperine-loaded mixed micelles (RES-P-MM) composed of Poloxamer 407 and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), in order to enhance its solubility, oral bioavailability and anticancer potency in comparison with RES loaded mixed micelles (RES-MM) and pure RES. RES-P-MM exhibited small particle size, good encapsulation efficiency, good stability in media simulating the physiological conditions of the gastrointestinal tract, and biocompatibility with no sign of tissue toxicity. Oral bioavailability of RES from RES-P-MM and RES-MM was increased by 5.7 and 2 fold compared to pure RES, respectively, while long circulation time and slow plasma elimination were observed, due to the metabolism inhibition effect of piperine. Moreover, RES-P-MM demonstrated higher in vitro anticancer activity in human breast cancer MCF-7 cells. The concentration of the drug needed for the growth inhibition of 50% of cells in a designated time period (GI50) was 7.97 ± 0.56 μg mL−1 for pure RES, while this was decreased by 79.42% for the RES-MM. Remarkably, the GI50 value for the RES-P-MM was 0.55 ± 0.29 μg mL−1, i.e., a 93.09% decrease compared with pure RES. Therefore, the developed mixed micelles containing piperine can act as a promising carrier system for hydrophobic anticancer drugs that have poor oral absorption and extensive metabolism such as RES, and can offer significant improvement in their oral bioavailability.

Andrographolide (AN), a diterpenoid lactone, is one of the prime phytoconstituents of Andrographis paniculata. AN possesses various therapeutic benefits such as hepatoprotective, analgesic, anti-inflammatory, anti-tumor, anti-hyperglycemic, anti-oxidant activities. However, AN has not reached its milestone therapeutic potential as clinical studies have suggested that a conventional dosage form of AN showed low oral bioavailability (2.67%). The factors attributed to low bioavailability included specific site absorption, hydrolysis in weak alkaline environments, first pass metabolism, P-gp excretion in the terminal intestine, biliary excretion and poor aqueous solubility (3.29 μg mL−1). A successful AN therapy warrants an apt delivery system that will enhance its bioavailability. Current approaches for developing an improved delivery system for AN are mainly focused on overcoming solubility and toxicity issues. The path to identify new molecules with better therapeutic efficacy will continue to be an integral part of health care systems but here the authors have emphasized on ‘better delivery of drugs’, which is going to further refine therapy. The different formulation approaches investigated so far have shown much promise experimentally in improving the bioavailability of AN. However, a product for human use is still far away. Since its isolation and characterisation in 1911 several developments related to AN have occurred. This review is the first comprehensive account of the pharmaceutical aspects of AN with special emphasis on its delivery that have occurred over the last century.

The aim of the study was to develop plumbagin (PLB) loaded D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS1k or TPGS)-folic acid conjugated nanomicelles (denoted as PTFM) to achieve controlled and targeted delivery with synergized anticancer potency and reduced PLB toxicity. PLB loaded TPGS micelles without folic acid conjugation (denoted as PTM) and PTFM were smaller in size and good encapsulation efficiency. The critical micellar concentration of TPGS-folic acid micellar solution was 0.015 mg ml−1. The micelles demonstrated sustained release and biocompatibility in hemolytic toxicity assay. Bioavailability of PLB from PTM and PTFM was increased by 3.9 and 4.8 fold with long circulation time, slower plasma elimination and no sign of blood and tissue toxicity as compared to free PLB. Moreover, formulated micelles demonstrated higher in vitro anticancer activity in folate over expressed human breast cancer MCF-7 cells. The targeting effect for the PTFM was also demonstrated. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 13.15 ± 1.31 μg ml−1 for PLB while it was decreased by 40.68% for the PTM. Furthermore, the GI50 value of PTFM was 3.2 ± 0.4 μg ml−1, i.e., a 75.67% decrease was observed as compared to free PLB. A synergistic effect of TPGS and PLB was also achieved which reveals a new concept of a polymeric micellar drug delivery system where a carrier having therapeutic effects brings about a reduction in dose as well as cost.

Plumbagin (PLB), a member of the quinine family, mainly found in the plant Plumbago zeylanica Linn., potentially exhibit anticancer, anti-inflammatory, anti-oxidant, antifungal, neuroprotective, hypolipidemic and antibacterial activities. However, it has been well known that the application of PLB was limited owing to its water insolubility, instability and poor bioavailability. For decades, many attempts have been made to compensate for these disadvantages with the development of improved delivery platforms as the feasible approaches. This review aims to describe the various studies supporting the biopharmaceutical aspects of PLB. In addition, it includes a section devoted to discussing the challenges associated with the drug and strategies to improve the properties of PLB such as solubility, stability and bioavailability. Also, this paper summarizes the recent works on the design and development of novel delivery systems of PLB such as liposomes, niosomes, microsphares, nanoparticles, micelles, complexization, metal nanoparticles, crystals modification, etc., with the goal of harnessing the true difficulties of this multifunctional agent in the clinical arena.

The aim of the present work was to design gellan gum and calcium carbonate based floating in situ gel as an efficient anti-ulcer formulation using andrographolide (AG) as a model drug. A 32 factorial design was used to study the effect of gellan gum and calcium carbonate on characteristic of in situ gelling system. The formulations were evaluated in terms of in vitro, in vivo anti-ulcer and histopathological study in Wistar rats. Drug content and viscosity were found in the range of 74.3 ± 1.2–95.5 ± 1.8% and 67.7 ± 1.6 to 152.13 ± 1.1 cps, respectively. Formulation gelled within 2 s and floated more than 24 h in simulated gastric fluid; an initial burst release of 11.7 ± 0.9 to 32.4 ± 2.1% till 1 h followed by a sustained release was observed. In vivo, the AG floating in situ gel (AGFIG) demonstrated lower acid and protein level, high hemoglobin level and negligible ulcer index. Moreover, it preserved integrity and histological aspects of the gastric mucosa as compared to pure AG and ranitidine. Improved anti-ulcer activity of AGFIG was attributed to longer residence time of AG in the stomach which improved the activity of myeloperoxidase, lipid peroxide, mucin content and glutathione peroxidase on gastric mucosal surface leading to protection from alcohol induced erosion. The study concluded that such floating in situ gelling system can be translated for existing and established anti-ulcer drugs.

Cochleates, a type of lipid based drug delivery system, are solid particulates made up of large continuous lipid bilayer sheets rolled up in a spiral structure with little or no internal aqueous phase. These nano-sized or sub-micron sized structures are generated on fusion of negatively charged liposomes with metal cations. They are efficient in encapsulating drug molecules that are hydrophobic and hydrophilic; positively charged as well as negatively charged. The interior of a cochleate structure remains substantially intact irrespective of outer harsh environmental conditions or enzymes. Cochleate technology is applicable for administration through parenteral, topical as well as oral routes and can be formulated in liquid or powder form. Cochleates have been reported to improve the oral bioavailability; improve the safety of the drugs by decreasing side effects and increasing drug efficacy; all of which lead to enhanced patient compliance. This review article highlights the important aspects of cochleates such as their structure, properties, methods of preparation, stability, advantages, applications and current status. The information provided herein should help formulators in judiciously selecting cochleate technology for delivery of drugs.

BACKGROUND Current therapy for pulmonary arterial hypertension (PAH) is unable to prevent progression of disease due to continuous infusions and multiple oral administrations. This resulted in the need of novel treatment which would target directly structural vascular changes that weaken blood flow through pulmonary circulation. OBJECTIVE The objective of present study was to develop spray dried (SD) formulation for dry powder inhaler (DPI) with enhanced aerosol performance and lung deposition by using novel bioactive, andrographolide (AGP) and carrier, scleroglucan (SCLG) with improved antihypertensive activity. The SDAGP formulation was evaluated for physicochemical properties and in vitro/in vivo lung deposition. Further, antihypertensive activity was studied by monocrotaline (MCT) induced rat model. RESULTS The SDAGP exhibited mean median aerodynamic diameter (MMAD) and fine particle fraction (FPF) of 3.37 ± 0.47 µm and 60.24 ± 0.98%. The in vivo absorption profile of final formulation reflected increased lung deposition of AGP at the end of 24 h with no signs of inflammation and toxicity. Moreover, SDAGP formulation confirmed enhanced antihypertensive activity. CONCLUSION The results proved use of AGP and SCLG as a novel bioactive and carrier with enhanced lung deposition and pulmonary antihypertensive activity.

The present work aimed at development of ranolazine loaded floating biomaterial gellan beads to enhance its site specific absorption. The beads obtained by ionotropic gelation method using sodium bicarbonate as gas-forming agent, calcium chloride and chitosan as a crosslinker were evaluated for physicochemical properties and in vitro performance. Yield and entrapment efficiency varied from 90 to 97% and 58 to 81% respectively. Surface topography revealed spherical microparticles with evenly distributed pores. Differential scanning calorimetry and powder X-ray diffraction pointed out amorphous nature of the drug. Effect of formulation variables on floating lag time and time required for 50% drug release was studied using Box-Behnken factorial design. The beads displayed good in vitro floatability in 0·1 N HCl with initial burst release followed by a controlled release up to 10 h whereas slow drug release was observed in phosphate buffer pH 6·8; probably due to decreased drug solubility and accelerated inte...

Paclitaxel (PTX), an antineoplastic bioactive, its clinical applications were hampered by its poor biopharmaceutical properties. There is need of safe, therapeutically effective and patient compliant drug delivery system. Clay minerals play a very crucial role in modulating drug delivery. The study deals with the investigation of a chitosan (CS) coated interlayer gallery of Na+ clay montmorillonite (MMT) and cationic paclitaxel (PTX) as a new drug delivery device to overcome PTX toxicity and enhance its therapeutic efficacy. PTX was intercalated into an interlayer gallery of MMT by an ion exchange reaction. Effect of different reaction conditions like time, pH and initial drug concentration on intercalation were studied. Optimised PTX-MMT hybrid nanocomposites were coated with biopolymer CS to get PTX-MMT-CS nanocomposites and characterised. Optimum intercalation (57·75%) of PTX molecules within the interlayer space of MMT was achieved with the pH of 6 at 3 h for 120 mg of PTX. The X-ray diffracti...

Background: The aim of the study was to investigate ethyl cellulose microsponges as topical carriers for the controlled release and cutaneous drug deposition of eberconazole nitrate (EB). Materials & method: EB microsponges were prepared using the quasiemulsion solvent diffusion method. The effect of formulation variables (drug:polymer ratio, internal phase volume and amount of emulsifier) and process variables (stirring time and stirring speed) on the physical characteristics of microsponges were investigated. The optimized microsponges were dispersed into a hydrogel and evaluated. Results & discussion: Spherical and porous EB microsponge particles were obtained. The optimized microsponges possessed particle size, drug content and entrapment efficiency of 24.5 µm, 43.31% and 91.44%, respectively. Microsponge-loaded gels demonstrated controlled release, nonirritancy to rat skin and antifungal activity. An in vivo skin deposition study demonstrated fourfold higher retention in the stratum corneum layer as compared with commercial cream. Conclusion: Developed ethyl cellulose microsponges could be potential pharmaceutical topical carriers of EB in antifungal therapy.

Budesonide, an inhaled glucocorticoid, is used for the treatment of large and small calibre airway inflammation associated with asthma. Conventional dry powder inhalers (DPIs) show least deposition efficiency in the lung due to agglomeration, increased particle size and minimum fluidisation. There is a need for controlled release budesonide DPI in order to improve maximum lung deposition with least toxicity and improve patient compliance. Budesonide loaded biopolymer based microparticles were prepared by controlled gelation of sodium alginate using calcium chloride and chitosan. Microparticles were evaluated for physical characteristics, in vitro lung deposition by Andersen cascade impactor and in vivo regional lung deposition by fabricated apparatus with measured respiratory minute volume of rats from plethysmography. The effect of DPI on the histology of lung tissues was also studied. The particle size, encapsulation efficiency, ζ potential, mass median aerodynamic diameter and fine particle fra...

Background: Phospholipid and Tween® 80 mixed micelles were investigated as injectable nanocarriers for the natural anticancer compound, plumbagin (PBG), with the aim to improve anticancer efficiency. PBG-loaded mixed micelles were fabricated by self-assembly; composition being optimized using 32 factorial design. Results & discussion: Optimized mixed micelles were spherical and 46 nm in size. Zeta potential, drug loading and encapsulation efficiency were 5.04 mV, 91.21 and 98.38% respectively. Micelles demonstrated sustained release of PBG. Micelles caused a 2.1-fold enhancement in vitro antitumor activity of PBG towards MCF-7 cells. Micelles proved safe for intravenous injection as PBG was stable at high pH; micelle size and encapsulation efficiency were retained upon dilution. Conclusion: Developed mixed micelles proved potential nanocarriers for PBG in cancer chemotherapy.

Andrographolide, a diterpene bioactive of Andrographis paniculata (Acanthaceae family), has long been used in India and China as a complimentary medicine. Yet, there is no detailed toxicological information to guarantee its safe use. In the present study, acute and subacute toxicity of andrographolide was assessed via oral route on rodents. In acute toxicity tests, mice (n = 6/group/sex) received andrographolide at oral doses of 1, 2, 3, 4, and 5 g/kg, whereas in subacute acute tests Wistar rats (n = 6/group/sex) received 250 and 500 mg/kg for 21 consecutive days. Hematological, biochemical, and histological analysis were performed in all animals. No death or hazardous signs were observed from acute toxicity study indicating that the LD50 of andrographolide by oral treatment was greater than 5 g/kg body weight in both male and female mice. No significant changes in body weight gain, food intake, behavior, mortality, hematological, biochemical, vital organ weight, and histopathology were observed from subacute toxicity study. However, a significant increase in white blood corpuscle (WBC) (7–14 %) and lymphocyte (21–24 %) counts coupled with a reduction in urea (17–24 %) suggested immune-stimulant and renal protective activity of andrographolide. The data support the safety of andrographolide which assure its medicinal use as an alternative medicine.

Introduction Plumbagin, a natural compound, is used as a complementary and alternative medicine. Isolation of plumbagin from Plumbago zeylanica by TLC and column chromatographic technique had various shortcomings. The objective of this work was to isolate plumbagin from roots of P. zeylanica by rapid and efficient method. Methodology The roots of P. zeylanica were cold macerated with a mixture of chloroform/dichloromethane (1:1) and the extract was successively washed with water, saturated sodium bicarbonate and water. The concentrated washed extract was dissolved in n-hexane and recrystallized to get plumbagin. The isolated and standard plumbagin was subjected to DSC, HPTLC, UV, FTIR, 1 H and 13 C NMR and mass spectroscopy studies for assessment of chemical structure and purity. Results The cold maceration yielded 1.2% (w/w) fine crystalline orange needle of plumbagin. It showed melting point at 78.4 °C, R f value at 0.64 in n-hexane:benzene (1:9) solvent system, UV absorption maxima at 417 nm and molecular peak [M+H] + at 188.20 m / z . Discussion Mass spectra and 13 C NMR confirmed the isolated compound structure which was supported by 1 H NMR. All the spectral data were comparable with that of reference standard. These results indicate that plumbagin can be isolated in a pure form effectively using cold maceration.

Andrographolide, a major bioactive phytoconstituent derived from Androgaphis paniculata that is safe and beneficial in several ailments, was formulated into pH-sensitive nanoparticle suspension with a view of improving its oral bioavailability. The andrographolide-loaded pH-sensitive nanoparticles were prepared by nanoprecipitation technique using Eudragit® EPO (cationic poly methacrylate copolymer). The 3(2) factorial design was used to optimize the amount of polymer and stabilizer (Pluronic® F-68). The optimized batch obtained using 0.45% w/v of Eudragit® EPO and 0.6% w/v of Pluronic® F-68 showed high-encapsulation efficiency of 93.8±0.67% with particle size of 255±9 nm and zeta potential of 29.3±3.4 mV. The bioavailability of andrographolide from optimized nanoparticles and pure andrographolide was assessed in male Wistar albino rats at a dose of 10 mg/kg. As compared to the pure andrographolide, almost 2.2 and 3.2-fold increase in AUC0-∞, Cmax and 121.53% increase in relative bioavailability were observed for andrographolide from pH-sensitive nanoparticles (P

The purpose of the present work was the development and evaluation of stomach-specific controlled release mucoadhesive drug delivery system prepared by ionotropic gelation of gellan beads, containing acid-soluble drug amoxicillin trihydrate, using 3(2) factorial design with concentration of gellan gum and quantity of drug as variables. The study showed that beads prepared in alkaline cross-linking medium have higher entrapment efficiency than the acidic cross-linking medium. The entrapment efficiency was in the range of 32% to 46% w/w in acidic medium, which increased up to 60% to 90% w/w in alkaline medium. Batches with lowest, medium, and highest drug entrapment were subjected to chitosan coating to form a polyelectrolyte complex film. As polymer concentration increases, entrapment efficiency and particle size increases. Scanning electron microscopy revealed spherical but rough surface due to leaching of drug in acidic cross-linking solution, dense spherical structure in alkaline cross-linking solution, and rough surface of chitosan-coated beads with minor wrinkles. The in vitro drug release up to 7 h in a controlled manner following the Peppas model (r = 0.9998). In vitro and in vivo mucoadhesivity study showed that beads have good mucoadhesivity and more than 85% beads remained adhered to stomach mucosa of albino rat even after 7 h. In vitro growth inhibition study showed complete eradication of Helicobacter pylori. These results indicate that stomach-specific controlled release mucoadhesive system of amoxicillin gellan beads may be useful in H. pylori treatment.

The purpose of this research work was to explore an application of uncoated porous drug carrier prepared by single-step drug adsorption for a delivery system based on integration of floating and pulsatile principles intended for chronotherapy. This objective was achieved by utilizing 3(2) factorial design, solvent volume (X(1)) and drug amount (X(2)) as selected variables, for drug adsorption using solvents, methanol, and dichloromethane (DCM), of varying polarity. Nitrogen adsorption (N(2)), scanning electron microscopy of cross-sections, and atomic force microscopy were done to study adsorption patterns and their effect on release pattern. Drug release study was customized by performing for 6 h in acidic environment to mimic gastroretention followed by basic environment akin to transit phase. Correlation between porous data from mercury and N(2) adsorption was probably studied for the first time. Observed regression analysis values for pore volume, surface area, and drug release indicated the influence of selected variables. Total release range in acidic medium was 12.77-24.57% for methanol, 8.79-15.26% for DCM, and final release of 69.45-92.23% for methanol, and 60.16-99.99% for DCM influenced by varying internal geometries was observed. Present form of drug delivery system devoid of any additives/excipients influencing drug release shows distinct behavior from other approaches/technologies in chronotherapy by (a) observing desired low drug release (8%) in acidic medium, (b) overcoming the limitations of process variables caused by multiple formulation steps and different characteristic polymers, (c) reducing time consumption due to single step process, and (d) extending as controlled/extended release.

Chronotherapy, a new approach for treating pathological conditions, is based on circadian rhythm. Present work conceptualizes a specific technology, based on combining floating and pulsatile principles to develop drug delivery system, intended for chronotherapy in arthritis. This approach was achieved by using low density microporous polypropylene, Accurel MP 1000 ® , as a multiparticulate carrier along with drug of choice ibuprofen. Carrier amount and solvent volume was kept invariant in designing this simple system by adsorbing drug via melting or solvent evaporation using different carrier: drug ratios. In solvent evaporation, methanol (M) and dichloromethane (DCM) were used. Drug loaded multiparticulate system was subjected to various characterization and evaluation parameters showing influence of adsorption process. Drug release study was performed in acidic environment using pH 1.2 HCl IP medium for 6 h to mimic gastric condition for evaluating gastroretention followed by basic environment using appropriate medium as phosphate buffer pH 7.2 IP for 3 h resembling transit. The release pattern showed influence of drug adsorption methods characterized by ever changing pore geometry with total release ranges in acidic medium as 10.7–27.6% and final release as 55.6–88.6%. Present drug delivery system devoid of any additives/excipients influencing drug release show distinct behaviour from other approaches/technologies in chronotherapy by (a) observing desired low drug release (11%) in acidic medium (b) overcoming the limitations of process variables caused by multiple formulation steps (c) reducing time consumption due to single step process (d) can be extended to controlled release also.

Low density porous carriers are widely used in the pharmaceutical applications. Response surface methodology, using 3(2) factorial design was used to study drug adsorption on and its release patterns from microporous polypropylene (Accurel MP 1000) in the absence of additives. Ibuprofen, as model drug, was adsorbed on the polymer by solvent evaporation using two organic solvents methanol (M) and dichloromethane (DCM). The amount of carrier (100 mg) and its particle size range (250-350 microm) were kept invariant while solvent volume (X1) and drug amount (X2) were taken as variables. Drug adsorption pattern depended on the type and amount of solvent used. DSC, XRD, FTIR and TGA, predict crystalline nature and physical form of adsorption. SEM showed the penetration and adsorption of the drug in and on the microporous polymer. Accurel MP 1000 had a pore volume of 1.992 g/cm3 and surface area of 55.9855 m2/g as detected by mercury porosimetery. On drug adsorption, pore volume ranged from 0.413 to 1.198 g/cm3 for methanol and 0.280-0.759 g/cm3 for DCM. Similarly surface area was in the range 38.445-25.497 m2/g for methanol and 18.710-32.528m2/g for DCM. The drug release was investigated in phosphate buffer pH 7.2. All batches showed excellent in vitro floating property. Drug release was partial with recovery to complete dependent on type and volume of solvent. R2 values relating to bulk density, pore volume, surface area and drug release at 60, 120 and 180 min were estimated. Effect of solvent properties shows a positive influence on drug adsorption and release. Release profiles of some batches could be considered as gastroretentive drug delivery system.

A blend of floating and pulsatile principles of drug delivery system would have the advantage that a drug can be released in the upper GI tract after a definite time period of no drug release. A multiparticulate floating-pulsatile drug delivery system was developed using porous calcium silicate (Florite RE®) and sodium alginate, for time and site specific drug release of meloxicam. Meloxicam was adsorbed on the Florite RE® (FLR) by fast evaporation of solvent from drug solution containing dispersed FLR. Drug adsorbed FLR powder was used to prepare calcium alginate beads by ionotropic gelation method, using 32 factorial design. Developed formulations were evaluated for yield, entrapment efficiency, image analysis, surface topography, mechanical strength, apparent density, buoyancy studies and dissolution studies. Entrapment efficiency of different formulations varied from 70% to 94%. Formulations show a lag period ranging from 1.9 to 7.8 h in acidic medium followed by rapid release of meloxicam in simulated intestinal fluid USP, without enzymes (SIF). Complete drug release in SIF occurred in less than 1 h from the formulations. The size of beads varied from 2.0 to 2.7 mm for different batches. Prepared beads were spherical with crushing strength ranging from 182 to 1073 g. Floating time was controlled by density of beads and hydrophobic character of drug. A pulsatile release of meloxicam was demonstrated by a simple drug delivery system which could be useful in chronopharmacotherapy of rheumatoid arthritis.

The purpose of the present study was characterization of microparticles obtained by adsorption of poorly water soluble drug, meloxicam, on a porous silicate carrier Florite RE (FLR) and development of a tablet formulation using these microparticles, with improved drug dissolution properties. The study also reveals the use of FLR as a pharmaceutical excipient. Meloxicam was adsorbed on the FLR in 2 proportions (1:1 and 1:3), by fast evaporation of solvent from drug solution containing dispersed FLR. Drug adsorbed FLR microparticles were evaluated for surface topography, thermal analysis, X-ray diffraction properties, infrared spectrum, residual solvent, micromeritic properties, drug content, solubility, and dissolution studies. Microparticles showed bulk density in the range of 0.10 to 0.12 g/cm(3). Dissolution of drug from microparticles containing 1:3, drug:FLR ratio was faster than microparticles containing 1:1, drug:FLR ratio. These microparticles were used for formulating directly compressible tablets. Prepared tablets were compared with a commercial tablet. All the prepared tablets showed acceptable mechanical properties. Disintegration time of prepared tablets was in the range of 18 to 38 seconds, and drug dissolution was much faster in both acidic and basic medium from prepared tablets as compared with commercial tablet. The results suggest that FLR provides a large surface area for drug adsorption and also that a reduction in crystallinity of drug occurs. Increase in surface area and reduction in drug crystallinity result in improved drug dissolution from microparticles.