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This study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core–shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC50 value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site.

Nanostructured lipid carriers (NLCs) have been proven to significantly improve the bioavailability and efficacy of many drugs; however, they still have many limitations. These limitations could hinder their potential for enhancing the bioavailability of poorly water-soluble drugs and, therefore, require further amendments. From this perspective, we have investigated how the chitosanization and PEGylation of NLCs affected their ability to function as a delivery system for apixaban (APX). These surface modifications could enhance the ability of NLCs to improve the bioavailability and pharmacodynamic activity of the loaded drug. In vitro and in vivo studies were carried out to examine APX-loaded NLCs, chitosan-modified NLCs, and PEGylated NLCs. The three nanoarchitectures displayed a Higuchi-diffusion release pattern in vitro, in addition to having their vesicular outline proven via electron microscopy. PEGylated and chitosanized NLCs retained good stability over 3 months, versus the nonPEGylated and nonchitosanized NLCs. Interestingly, APX-loaded chitosan-modified NLCs displayed better stability than the APX-loaded PEGylated NLCs, in terms of mean vesicle size after 90 days. On the other hand, the absorption profile of APX (AUC0-inf) in rats pretreated with APX-loaded PEGylated NLCs (108.59 µg·mL−1·h−1) was significantly higher than the AUC0-inf of APX in rats pretreated with APX-loaded chitosan-modified NLCs (93.397 µg·mL−1·h−1), and both were also significantly higher than AUC0-inf of APX-Loaded NLCs (55.435 µg·mL−1·h−1). Chitosan-coated NLCs enhanced APX anticoagulant activity with increased prothrombin time and activated partial thromboplastin time by 1.6- and 1.55-folds, respectively, compared to unmodified NLCs, and by 1.23- and 1.37-folds, respectively, compared to PEGylated NLCs. The PEGylation and chitosanization of NLCs enhanced the bioavailability and anticoagulant activity of APX over the nonmodified NLCs; this highlighted the importance of both approaches.

The main purpose of this study was to develop and evaluate solid self-nanoemulsifying drug delivery systems (S-SNEDDs) of Atorvastatin/ Ezetimibe combination to combine the advantages of liquid SNEDDs with those of solid dosage forms and investigate the effect of solidification on both lipid lowering efficiency and the ability to enhance oral bioavailability of included poorly water soluble drugs. Spray dried solid powder was prepared using Aerosil 200 based on its high adsorption capacity and the ratio of liquid SNEDDs: Aerosil was (4:1) due to the smaller droplet size produced after reconstitution compared to other ratios. Surface morphology characteristics and drug-excipients interactions were evaluated via Scanning Electron Microscopy (SEM) and Fourier Transformed Infrared Spectroscopy (FTIR). Crystallinity nature affect drug dissolution so, it was determined by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD). Pharmacokinetic study investigated the ability of (S-SNEDDS) to improve oral bioavailability of included drugs while, pharmacodynamic study evaluate its efficiency to control serum cholesterol levels compared to pure drugs suspension and liquid SNEDDs. Solid spray dried powder showed very good flowability (3.41±0.23g/s) and rapid dispersion in water with maintaining the self-emulsifying efficiency of liquid formula. Physicochemical evaluation of powder showed spherical separated particles with no significant drug-excipients interactions and drugs are molecularly dispersed or in amorphous state that improve dissolution rate as proven by in-vitro release studies. Pharmacokinetic and pharmacodynamic studies proved that the solidification process had no remarkable effect on the efficiency of liquid formula to enhance oral bioavailability of incorporated drugs and control serum cholesterol level compared to pure drugs suspension. S-SNEDDS was proved as efficient candidate to improve oral bioavailability of Atorvastatin / Ezetimibe combination and control cholesterol serum levels.

Objective: Ezetimibe (EMB) is a commonly used lipid-lowering medication that lowers cholesterol and triglycerides. Because of its lower water solubility and hepatic metabolism, it necessitates the formulation of drug delivery systems that are capable of improving solubility and avoiding hepatic effect. Methods: Ezetimibe nanostructured lipid carriers (EMB-NLCs) were formulated and examined. They were formulated through emulsification with a high homogenization speed and ultrasonication (The method and evaluation parameters have been mentioned under method section in Formulation of EMB-NLCs paragraph). Results: The formulated NLCs have exhibited particle size (P. S.) between 163.6±7.20 and 866.66±18.65 nm and the zeta potential (Z. P.) values have ranged between-24±1.25 and-35±0.25 mV. Besides, they exhibited higher EE% than 77 percent and the drug encapsulated in lipid matrix was in amorphous state. Pharmacokinetics of optimized formula (F1; composed of 2% w/w Gelucire® 43/01, 8% w/w Miglyol® 812 N, 0.5% w/w lecithin and 2% w/w Poloxmer® 188) have exhibited 2.63-and 2.33-fold increase in oral bioavailability in comparison with EMB suspension and marketing product (Ezetrol® 10 mg tablet), respectively. Conclusion: These studies have demonstrated that, NLCs are superior for enhancing in vivo behavior and oral bioavailability of EMB.

This research aims to develop a drug delivery system that effectively treats colitis while administering curcumin/mesalamine by coating alginate/chitosan beads with Eudragit® S-100 to target the colon. Beads were tested to determine their physicochemical characteristics. Coating with Eudragit® S-100 prevents drug release at a pH of less than 7; this was demonstrated by in-vitro release conducted in a medium with gradually varying pH to mimic circumstances in various regions of the gastrointestinal tract. This study examined the efficacy of the coated beads in treating acetic acid-induced colitis in rats. Results showed that spherical beads were formed with an average diameter of 1.6–2.8 mm, and the obtained swelling ranged from 409.80% to 890.19%. The calculated entrapment efficiency ranged from 87.49% to 97.89%. The optimized formula F13 (which was composed of mesalamine-curcumin active ingredients, Sodium alginate as a gelling agent, chitosan as a controlled release agent, CaCl2 as a crosslinking agent, and Eudragit S-100 as a pH-sensitive coating agent) demonstrated the best entrapment efficiency (97.89% ± 1.66), swelling (890.19% ± 60.1), and bead size (2.7 ± 0.62 mm). In formulation #13, which was coated with Eudragit S 100, curcumin (6.01 ± 0.04%) and mesalamine (8.64 ± 0.7%), were released after 2 h at pH 1.2; 6.36 ± 0.11% and 10.45 ± 1.52% of curcumin and mesalamine, respectively, were then released after 4 h and at pH 6.8. Meanwhile, at pH 7.4, after 24 h, approximately 85.34 ± 2.3% (curcumin) and 91.5 ± 1.2% (mesalamine) were released. Formula #13 significantly reduced the colitis, and this suggests that the developed hydrogel beads can be used for delivering curcumin-mesalamine combinations to treat ulcerative colitis after adequate research.

Apixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier (NLC) to increase its bioavailability and effectiveness. As solid lipid, liquid lipid, hydrophilic, and lipophilic stabilizers, stearic acid, oleic acid, Tween 80, and lecithin were used, respectively. Utilizing Box–Behnken design, the effects of three factors on NLC particle size (Y1), zeta potential (Y2), and entrapment efficiency percent (Y3) were examined and optimized. The optimized formula was prepared, characterized, morphologically studied, and pharmacokinetically and pharmacodynamically assessed. The observed responses of the optimized Apx formula were 315.2 nm, −43.4 mV, and 89.84% for Y1, Y2, and Y3, respectively. Electron microscopy revealed the homogenous spherical shape of the NLC particles. The in vivo pharmacokinetic study conducted in male Wistar rats displayed an increase in AUC and Cmax by 8 and 2.67 folds, respectively, compared to oral Apx suspension. Moreover, the half-life was increased by 1.94 folds, and clearance was diminished by about 8 folds, which makes the NLC formula a promising sustained release system. Interestingly, the pharmacodynamic results displayed the superior effect of the optimized formula over the drug suspension with prolongation in the cuticle bleeding time. Moreover, both prothrombin time and activated partial thromboplastin time are significantly increased. So, incorporating Apx in an NLC formula significantly enhanced its oral bioavailability and pharmacodynamic activity.

Purpose: To synthesize novel pyridine derivatives and evaluate their efficiency as potent inhibitors of cyclin dependent kinase 2 (CDK2) enzyme for cancer therapy.Methods: Pyridine scaffold were synthesized using one-pot multicomponent condensation reaction of arylidine with different primary amines. The cytotoxic potential of the new compounds was assessed using various cell lines. Furthermore, molecular docking studies based on the crystal structure of CDK2 was carried out to determine the possible binding modes that influence the anticancer activities.Results: The results indicate that one-pot multicomponent reaction generated a series of functionalized pyridines with good yield. In vitro cytotoxicity study revealed superior cytotoxicity of the designed compounds against prostate and cervical cancer cell lines compared to 5-fluorouracil (standard anticancer compound) with half-maximal inhibitory concentration (IC50) values of 0.1 – 0.85 and 1.2 –74.1 μM, respectively. Finally, molecular modeling simulation of the newly synthesized compounds showed that they fit well and are stabilized into CDK2 active site via hydrogen bonding and hydrophobic interactions.Conclusion: The results indicate that the newly synthesized pyridine can exert potent anticancer activity presumably via inhibition of CDK2. However, this will need to be confirmed in in vivo studies.

This work aimed to establish a simple method to produce additive-free triamcinolone acetonide (TAA) microspheres suitable for pulmonary delivery, and therefore more simple manufacturing steps will be warranted. The spray-drying process involved the optimization of the TAA feed ratio in a concentration range of 1–3% w/v from different ethanol/water compositions with/without adding ammonium bicarbonate as a blowing agent. Characterization of the formulas was performed via scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction. Our results indicated that the size and morphology of spray-dried TAA particles were dependent on the feed and solvent concentrations in the spray-dried formulations. Furthermore, adding the blowing agent, ammonium bicarbonate, did not produce a significant enhancement in particle characteristics. We prepared additive-free TAA microspheres and found that TAA formulation #1 had optimal physical properties in terms of diameter (2.24 ± 0.27 µm), bulk density (0.95 ± 0.05), tapped density (1.18 ± 0.07), and flowability for deposition during the pulmonary tract, from a centric airway to the alveoli as indicated by Carr’s index = 19 ± 0.01. Hence, formulation #1 was selected to be tested for pharmacokinetic characters. Rats received pulmonary doses of TAA formula #1 and then the TTA concentration in plasma, fluid broncho-alveolar lavage, and lung tissues was determined by HPLC. The TAA concentration at 15 min was 0.55 ± 0.02 µg/mL in plasma, 16.74 ± 2 µg/mL in bronchoalveolar lavage, and 8.96 ± 0.65 µg/mL in lung homogenates, while at the 24 h time point, the TAA concentration was 0.03 ± 0.02 µg/mL in plasma, 1.48 ± 0.27 µg/mL in bronchoalveolar lavage, and 3.79 ± 0.33 µg/mL in lung homogenates. We found that TAA remained in curative concentrations in the rat lung tissues for at least 24 h after pulmonary administration. Therefore, we can conclude that additive-free spray-dried TAA microspheres were promising for treating lung diseases. The current novel preparation technology has applications in the design of preparations for TAA or other therapeutic agents designed for pulmonary delivery.

The current work aimed at adopting in situ combination of sono-precipitation and alkali hydrolysis as a rapid technique for starch nanoparticles (SNPs) preparation under ambient conditions with a high yield. Factors affecting the preparation of SNPs were investigated based on statistical analysis using the Box Behnken design. The particle size and polydispersity index of particles were used as dependent variables to obtain the optimized formulation. The SNPs optimized formulation (F14) was further characterized for zeta potential, transmission electron microscopy, Fourier transform infrared spectroscopy, differential thermal analysis and X-ray diffraction. The results of particle size were between 44.82±3.31 and 83.93±8.53 while polydispersity index results were ranged from 0.106±0.012 to 0.179±0.018. The results obtained revealed the efficiency of the technique in obtaining a high yield (98.72% ±0.89) of well-distributed nanoparticles. Also, the SNPs obtained were spherical in shape with good stability, as indicated by zeta analysis (-20±0.25mV) and thermal analysis. The data obtained also showed no change in the chemical structure of the SNPs, as indicated by the infrared transmission of Fourier, thermal analysis, and the relative crystallinity of SNPs was decreased compared with native maize starch indicating the crystallite is transformed from crystalline to amorphous form. The obtained results concluded the efficiency of the adopted method on obtaining SNPs in a short preparation time with a high yield under ambient conditions.

Purpose This research aimed to improve water solubility and oral bioavailability of a newly synthesized thienopyrimidine derivative (TPD) with anti-pancreatic cancer activity by loading on starch nanoparticles (SNPs). Methods TPD was synthesized, purified and its ADME behavior was predicted using Swiss ADME software. A UV spectroscopy method was developed and validated to measure TPD concentration at various dosage forms. SNPs loaded with TPD (SNPs-TPD) were prepared, characterized for particle size, polydispersity index, zeta potential, transmission electron microscopy, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), entrapment efficiency, in-vitro release, and in-vivo animal study. Results The Swiss ADME results showed that TPD can be administered orally; however, it has low oral bioavailability (0.55) and poor water solubility. The significant regression coefficient of the calibration curve (r2 = 0.9995), the precision (%RSD < 0.5%) and the accuracy (99.46−101.72%) confirmed the efficacy of the developed UV method. SNPs-TPD had a spherical monodispersed (PDI= 0.12) shape, nanoparticle size (22.98 ± 4.23) and good stability (−21 ± 4.72 mV). Moreover, FT-IR and DSC revealed changes in the physicochemical structure of starch resulting in SNPs formation. The entrapment efficiency was 97% ± 0.45%, and the in-vitro release showed that the SNPs enhanced the solubility of the TPD. The in-vivo animal study and histopathology showed that SNPs enhanced the oral bioavailability of TPD against solid Ehrlich carcinoma. Conclusion SNPs-TPD were superior in drug solubility and oral bioavailability than those obtained from TPD suspension., Graphical Abstract

The objective of this study was to formulate and evaluate valsartan (VLT) ethosomes to prepare an optimized formula of VLT-entrapped ethosomes that could be incorporated into a sustained release transdermal gel dosage form. The formulation of the prepared ethosomal gel was investigated and subjected to in vitro drug release studies, ex vivo test, and in vivo studies to assess the effectiveness of ethosomal formulation in enhancing the bioavailability of VLT as a poorly soluble drug and in controlling its release from the transdermal gel dosage form. The acquired results are as follows: Dependent responses were particle size, polydispersity index, zeta potential, and entrapment efficiency. The optimized VLT-ETHs had a nanometric diameter (45.8 ± 0.5 nm), a negative surface charge (−51.4 ± 6.3 mV), and a high drug encapsulation (94.24 ± 0.2). The prepared VLT ethosomal gel (VLT-ethogel) showed a high peak plasma concentration and enhanced bioavailability in rats compared with the oral solution of valsartan presented in the higher AUC (0–∞). The AUC (0–∞) with oral treatment was 7.0 ± 2.94 (μg.h/mL), but the AUC (0–∞) with topical application of the VAL nanoethosomal gel was 137.2 ± 49.88 (μg.h/mL), providing the sustained release pattern of VLT from the tested ethosomal gel.

A niosomal formula of acemetacin was developed to improve its tumor targeting and radio-kinetic evaluation was performed using

This work aimed to elaborate an optimised fluticasone propionate (FP)-loaded solid lipid nanoparticles (SLNs) to enhance FP effectiveness for topical inflammatory remediation. The influences of drug amount, lipid, and surfactant ratios, on drug release pattern and stability were investigated utilising Box-Behnken design. Elaboration, characterisation, and pharmacodynamic evaluation in comparison with the marketed formulation (Cutivate® cream, 0.05%

Starch-based nanosystems are considered a talented nanocarrier for drug delivery owing to their small particle size, biodegradability, and biocompatibilities. Starch-based nanosystems showed enhancement in biological activity, solubility, entrapment efficiency, and in-vitro release of several drugs. Starch-based nanosystems are categorized into two types; starch nanocrystals and starch nanoparticles. The difference between starch nanocrystals and starch nanoparticles will be summarized. Numerous techniques are employed to formulate starch-based nanosystems including chemical and physical methods. This review summarizes the existing knowledge on; a number of techniques used to formulate starch-based nanosystems, factors affecting each technique, and the advantages of combining both physical and chemical methods on the formulation time and physicochemical properties of the starch-based nanosystems. Besides, most innovative information regarding starch-based nanosystems modification on increasing entrapment efficiency will be discussed. Furthermore, applying starch-based nanosystems as effective drug delivery nanocarriers for delivering drugs and bioactive elements to improve their bioavailability will be abridged in this review.

Microsponges are micro-porous particles, used mainly for topical and recently for oral administration. Microsponges have many advantages which make it a versatile drug delivery system. Microsponges can suspended or entrap a wide variety of substances and then be incorporated into a formulated product such as a gel, cream, liquid, or powder. Moreover, they may enhance stability, reduce side effects and modify drug release related to its porous structure which allows the active ingredient to sustain over time. This article aims to provide details about microsponges including the method of preparation, characterization, mechanism of drug release from microsponges, different formulation, and process factors, and a few applications about microsponges that are either proven or under research. Besides, microsponges improve stability, increase elegance, and enhance formulation flexibility. Previous studies were done and confirmed that microsponges are non-irritant, non-allergenic, non-mutagenic, and non-toxic. This technology is being used currently in cosmetics, sunscreens, and prescription products. Therefore, the microsponges based drug delivery technology is likely to become a valuable drug delivery matrix substance for various therapeutic applications in the future.

In this article, we offer a summary of a broad variety of colloidal drug delivery systems with a special emphasis on vesicular used in testing or theoretically useful as carrier systems for medicines or active biomolecules or as cell carriers with therapeutic use. They provide several significant details of the currently developed drug delivery systems for academic or clinical applications. This series of systems are commonly used due to outstanding drug tracking, continuous and regulated release behavior, improved drug molecules clogging performance, avoidance of product hydrolysis or enzymatic degradation, and therapeutic efficacy improvements. Such characteristics aid in the discovery of suitable carrier structures for the transmission of medicines, cells, and genes in various fields. Colloidal drug delivery systems play a significant role in drug delivery. In my opinion, all colloidal carriers present notable characteristics after application. These vesicles can deliver an active compound through the biological membranes via absorption, fusion, and to raise the quantity of permeated drugs compared with conventional formulations.

The skin is known to be the primary intact skin layer for the application of cosmetics and medicines. These nanocarriers, however, can enhance the distribution of molecules through hair follicles or impart a regulated pattern of release by making depots on the skin.. moreover, Many challenges may potentially face the topical delivery of medicaments through either the healthy or diseased skin. This is mainly owing to the strong protection offered by the barriers made of the skin. This paper displays the blocking nature of the skin, the difficult conditions of skin inflammatory diseases, options of effective treatment, and general categories of advanced topical drug delivery for better efficacy and safety. Solid lipid nanoparticles and other lipid-based nanocarriers are mentioned particularly with a further focus along with examples of opportunities for bioavailability enhancement of poorly absorbed active moieties and for more promising implementation in convenient and efficient topical remediation of skin inflammatory disorders.

Solid lipid nanoparticles (SLNs) are categorized as a novel generation of nanocarriers attracting huge attention as innovative colloidal carrier systems used for drug delivery as they integrate the advantages and avoid the disadvantages of other colloidal carries such as liposomes as well as polymeric nanoparticles. SLNs are biocompatible and biodegradable carrier system made from physiological lipids, which decrease the danger of cute and chronic toxicity. Moreover, SLNs have been used as a possible attractive drug-carrier for topical drug delivery. Drug delivery to the skin is widely used for local and systemic delivery and has potentials to be improved by application of nanoparticulate formulations. This review discus on many aspects of SLNs such as their advantages and disadvantages, method of preparation, excipients influence, SLNs and topical delivery and their therapeutic applications. SLNs are promising delivery carriers for lipophilic as well as hydrophilic drugs and can form a base in the field of modern pharmaceutics.

Solid lipid nanoparticles (SLN) are colloidal lipid carriers, which used for improving the bioavailability of lipophilic and hydrophilic drugs. SLN are composed of biodegradable lipids such as hard fats, highly purified triglycerides, monoglycerides, complex glyceride mixtures or waxes which are solid at room temperature. In the present study, different formulation variables, including the type and quantity of lipid and surfactant were optimized for the preparation of SLN. SLN were prepared by a modified micro emulsion-based method and their particle size was evaluated. Two types of surfactants Tween 80 and Poloxamer 188 were used. Also, the monoglyceride (Glyceryl monostearate) and wax (Cetyl palmitate) were used as lipid. The optimum SLN formulae were at lipid concentration 5%. The optimum surfactant concentration was 6%. SLN with a surfactant Tween 80 were smaller in size than Poloxamer 188 SLN. Glyceryl monostearate formed a smaller size SLN than Cetyl palmitate. Increasing Glyceryl monostearate concentration in the lipid ratio resulted in the formation of small size SLN.

The purpose of this investigation was to encapsulate carvedilol, a model beta-blocker antihypertensive into nano-spanlastics, followed by incorporation into 1% CMC wafer to afford a mucoadhesive buccal drug delivery system, targeting to sidestep the first-pass metabolism, improving the drug absorption and pharmacological effect, achieving non-invasive buccal delivery for treating hypertension. Carvedilol-loaded nano-spanlastics were rendered by ethanol injection technique, using 23 factorial design. The effect of formulation variables was investigated on nano-spanlastic characteristics. The optimal nano-spanlastic formulation (S2; containing 20% Brij 97) exhibited particle size (239.8 ± 5 nm), entrapment efficiency (98. 16 ± 1.44%), deformability index (8.74 ± 0.42 g), and the flux after 24 h (Jmax) (22.5 ± 0.25 (μg/cm2/h) with enhancement ratio 2.87 as well as excellent stability after storage. Permeation study verified the preeminence of the S2 formula. A confocal laser scanning microscope showed deep penetration of S2 through sheep buccal mucosa formula compared to rhodamine B solution. S2-based wafer showed acceptable characters (pH, swelling, drug content, residence time, and release rate). In vivo studies (pharmacodynamic study and biochemical evaluation) showed considerable improvement in blood pressure, the profile of the lipid, oxidant stress biomarkers, and cardiac markers. Histopathological studies revealed the superiority of S2 wafer in the protection of heart tissues over Carvid®. The results achieved indicate that nano-spanlastic-based wafer offers a promising improving trans-buccal carvedilol delivery system.

Introduction: The use of a mouthwash augments mechanical removal of plaque by brushing and flossing and helps maintain oral health through its antiplaque and antibacterial chemical properties. Aim: to evaluate and compare clinically and microbiologically the effectiveness of chlorhexidine and sodium hexametaphosphate mouth rinses on dental plaque in children. Materials and methods: This randomized clinical trial included 40 normal apparently healthy and cooperative children aged 8 to 10 years and selected from the Outpatient Dental Clinic of Pediatric dentistry Department, Faculty of Dentistry, Suez Canal University. Children were randomly divided into 2 groups as follows: Group I: included (20) children who rinsed with Chlorhexidine )0.2%) and Group II: included (20) children who rinsed with Sodium Hexametaphosphate (7% ). Clinical evaluation was performed by measuring gingival and plaque indices scores at all evaluation periods. Microbiological evaluation was performed by direct examination of bacterial cultures. Results: Sodium hexametaphosphate 7% mouth rinse showed a superior effect compared to chlorhexidine 0.2% mouth rinse in terms of improvement in the clinical scores and decreasing the microbial counting. Conclusion: Sodium hexametaphosphate 7% mouth rinse is a promising candidate of mouthwashes.

Nanosponges are colloidal carriers that potentially improve the aqueous solubility of poorly water-soluble drug, retarding its release, improving bioavailability, enhancing physical and chemical stability and decrease skin irritation as well. In addition, hydrogels and Nano-sponges are assumed to be excellent applicants for controlled release devices, bio-adhesive devices or target devices of therapeutic agents. Nanosponges may also be used to protect encapsulated molecules from light or from chemical and enzyme induced degradation, e.g. encapsulating 5-fluorouracile, a light-sensitive drug, in Nano-sponges protect it from light degradation, as well shelf life prolongation of camptothecin on encapsulation on Nano-sponges. Nano-sponges also protected the lactone ring from opening due to its high inclusion abilities, thereby increasing stability. Moreover, Nano-sponges can be used to design modified release product to provide slow, continuous delivery of the drug over the entire dosing interval. This makes it possible to decrease the dose administered, change the pharmacokinetic profile, and decrease side effects. Flurbiprofen, Doxorubicin were released slowly when incorporated in β-CD Nano-sponges. As well Nelfinavir mesylate, a protease inhibitor with low bioavailability, used to treat HIV infections, loaded Nano-sponges was prepared to enhance the solubility of the drug with slow release from Nano-sponges than from a β-CD complex.

Timolol maleate (TMM) is a hydrophilic model drug. The aim of this study was to formulate TMM-loaded microsponges to sustain TMM release and improve its corneal permeability compared with TMM-aqueous solution. The modified quasi-emulsion solvent diffusion technique (water/oil/oil) was used to prepare TMM-loaded microsponges. The impact of the polymer type (X1) and drug:polymer ratio (X2) were studied and optimized, using full factorial design. The production yield (PY) %, entrapment efficiency (EE) %, particles size (PS), and TMM released % after 6 h were selected as dependent variables. Depended on the desirability value by using the Design-Expert® software version 11, the optimized formulation was selected and subjected to further studies, such as scanning electron microscopy (SEM), porosity determination, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), ex vivo permeation study, and corneal hydration level. The optimized formulation composed of TMM: EC within the proportion 1:9 exhibited PY of 96.55 ± 4.01%; EE of 72.00 ± 6.08%; PS (d90) of 6283.33 ± 145.71 nm and released 42.12 ± 3.93% of TMM after 6 h. Particles appeared porous with spherical shape. Thermal analysis proved that the drug has been homogeneously dispersed in its amorphous state. The optimized formulation showed higher corneal permeability about 1.45-fold higher than TMM-aqueous solution in a period of 6 h. The modified quasi-emulsion diffusion technique (water/oil/oil) is suitable for improving EE of hydrophilic drug (TMM) and the optimized TMM-loaded microsponge was succeeded to retard the release of TMM and improve its corneal permeability.

Purpose: Carvedilol (CRV) is a non-selective beta-blocker used for hypertension treatment, angina pectoris, and heart failure. Oral administration of CRV showed poor bioavailability (25%), which may be due to exposure to the first-pass metabolism. Buccal delivery was used to boost its bioavailability.Methods: In this study carboxymethylcellulose/hydroxypropyl cellulose (CMC/HPC) composite buccal sponge enriched with CRV bilosomes was developed. Bilosomes were prepared using the thin-film hydration-sonication technique by applying a 32 -factorial design.Results: BL9 possessed the highest desirability value (0.861) and therefore, it was chosen as an optimal bilosomes. It exhibited a spherical shape with 217.2 nm, 87.13% entrapment efficiency, and a sustained release of CRV up to 24h. Consecutively, BL9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain a CMC-HPCL9 bilosomal sponge to enhance CRV buccal delivery. Morphological analysis of the prepared sponge with improved swelling showed a porosity of 67.58 percent. The in vivo assessment of rats indicates that the CMC-HPC/BL9 sponge enhances systolic/diastolic blood pressure, lipid profiles, oxidative stress biomarkers, and heart biomarkers with improved heart tissue quality.Conclusion: These results strongly encourage the use of this novel CMC-HPC/BL9 composite buccal sponge for the management of hypertension.

The purpose of this investigation was to encapsulate carvedilol, a model beta-blocker antihypertensive into nano-spanlastics, followed by incorporation into 1% CMC wafer to afford a mucoadhesive buccal drug delivery system, targeting to sidestep the first-pass metabolism, improving the drug absorption and pharmacological effect, achieving non-invasive buccal delivery for treating hypertension. Carvedilol-loaded nano-spanlastics were rendered by ethanol injection technique, using 2

Introduction: Betamethasone dipropionate is a highly effective corticosteroid anti-inflammatory. However, the main drawback of its topical use is the limited skin penetration into deeper skin layers. Also, its systemic use has shown many side effects. Objective: The goal of this research was to formulate betamethasone dipropionate in nanostructured lipid carriers (NLC) formulae that contain oleic acid to aid its penetration to deeper skin layers and to aid absorption to local regions upon topical application. Methods: NLC formulae were prepared by high shear homogenization then sonication. Formulae were characterized for their particle size, size distribution, electric potential, occlusion factor, entrapment efficiency, drug loading, transmission electron microscopy, in vitro drug release, and ex vivo skin penetration. Compatibility of ingredients with drug was tested using differential scanning calorimetry. Formulae were shown to have appropriate characteristics. NLC formulae were superior to traditional topical formulation in drug release. Results: Upon testing ex vivo skin penetration, betamethasone dipropionate prepared in NLC formulae was shown to penetrate more efficiently into skin layers than when formulated as a traditional cream. NLC formulation that contained higher percentage of oleic acid showed higher penetration and higher amount of drug to pass through skin. Conclusion: In general, NLC with lower oleic acid percentage was shown to deliver betamethasone dipropionate more efficiently into deeper skin layers while that of a higher oleic acid percentage was shown to deliver the drug more efficiently into deeper skin layers and through the skin, transdermally.

To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box–Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box–Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers.

The purpose of this study was to develop miconazole nitrate (MN) based solid lipid nano-carrier formulae for topical delivery to enhance its antifungal effectiveness. Miconazole nitrate loaded Solid lipid nanoparticles (MN-SLNs) were formulated using a high shear homogenization technique characterized by particle size, polydispersity index (PI), trapping efficiency (EE percent), drug loading (DL percent) and zeta potential (ZP) characteristics. Furthermore, the optimized formulae were investigated for in-vitro release, ex-vivo study, skin toxicity test, and antifungal activity. With a particle size range of 244.2 ± 27.2 nm to 493.6 ± 35.3 nm, the selected MN-SLNs were spherical shaped. A high EE product percentage ranging from 79.38 ± 2.35 percent to 95.92 ± 6.12 percent and Zeta potential ZP values ranging from-21.6 ± 7.05 mV to-31.4 ± 6.84 mV suggesting strong stability was achieved. A controlled release of MN from the SLNs up to 48 h was shown in-vitro release study. The ex-vivo study showed that the selected MN-SLN (F4) mixture exhibited higher MN flux in the skin than a 1% MN solution. Moreover, selected MN-SLN (F4) has demonstrated a higher zone of inhibition against Candida albicans than a simple drug solution. MN-SLN (F4) had the lowest toxicity value for the skin. Besides, the MN-SLNs (F4) substantially reported antifungal activity with the least histopathological improvements compared to MN-solution utilizing immune-suppressing albino rats with induced candidiasis fungal infection. It can be fulfilled that SLNs can be acquired as a promising carrier for topical delivery of poorly soluble MN.

Purpose This study aims to benefit from the capabilities of quality by design (QbD) and design of experiments (DoE) to develop and optimize nanostructured lipid carriers (NLCs) entrapping both Simvastatin (SIM) and Nifedipine (NIF) with the best formulation parameters through screening and optimization stages. Methods NLCs loaded with both SIM and NIF (SIM-NIF-NLCs) were prepared by emulsification evaporation method followed by homogenization. Different factors that may affect the NLCs characteristics were screened using D-optimal design. The effect of the most significant variables on the NLCs quality was optimized using a central composite design. The optimized SIM-NIF-NLCs were characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectrometry (FTIR). Furthermore, in vitro release and pharmacodynamics of the optimized NLCs formulation were studied. Results The optimized SIM-NIF-NLCs had a particle size of less than 200 nm and high entrapment efficiency. DSC results showed that SIM and NIF were completely incorporated in the lipids at an amorphous state. The pharmacodynamics study showed that the optimized SIM-NIF-NLCs have a great potential in lowering blood cholesterol levels compared to the individual drug suspensions with a dose reduction of both drugs. Conclusion This investigation revealed the potential use of both D optimal design and central composite design as valuable tools to recognize the most significant formulation variables as well as to optimize these variables to achieve NLCs with optimal characteristics.

Purpose This work aimed to investigate the release of poorly water-soluble drugs from microemulsion gel formulations using leflunomide and diclofenac combination as model drugs. Methods Combination treatment, immunomodulatory (leflunomide), and NSAIDs (diclofenac sodium) were developed and tested for active rheumatoid arthritis. Various surfactants and cosurfactants have been tested for their ability to emulsify the selected oil process. Pseudo ternary diagrams have been developed to describe the field of the microemulsion. The microemulsion was prepared using isopropyl myristate as oil phase, tween 80 as a surfactant, and 1-pentanol as co-surfactant were assessed for droplet size, poly dispersibility index, zeta potential. Results The average droplet size and zeta potential values for the selected formulation were 31.54 ± 5.37 nm and −7.14 ± 2.91, respectively. Optimized microemulsion systems were formulated into gel form to enhance the viscosity, carbopol was used to form a microemulsion gel evaluated for pH, spreadability, viscosity, drug content, differential scanning calorimetry, Fourier transforms infrared spectra analysis, and in vitro drug release using dialysis bag. For selected formulations, in vitro release has been studied and the F2C formula showed appropriate cumulative drug release (77.36% for leflunomide and 89.90% for diclofenac sodium) after 24 h. A 28-day anti-arthritic evaluation (body weight, paw edema, hematological parameters, and histopathology) on arthritic rat model showed significant relief of arthritis. Conclusions Transdermal formulation containing leflunomide and diclofenac is introduced as a gel-based on microemulsion has shown promising results and can be considered a suitable formula for the ME gel capable of achieving sustained release.

The aim of the current study is to establish a comprehensive experimental design for the screening and optimization of Atorvastatin-loaded nanostructured lipid carriers (AT-NLCs). Initially, combined D-optimal screening design was applied to find the most significant factors affecting AT-NLCs properties. The studied variables included mixtures of solid and liquid lipids, the solid/liquid lipid ratio, surfactant type and concentration, homogenization speed as well as sonication time. Then, the variables homogenization speed (A), the ratio of solid lipid/liquid lipid (B), and concentration of the surfactant (C) were optimized using a central composite design. Particle size, polydispersity index, zeta potential, and entrapment efficiency were chosen as dependent responses. The optimized AT-NLCs demonstrated a nanometric size (83.80 ± 1.13 nm), Polydispersity Index (0.38 ± 0.02), surface charge (−29.65 ± 0.65 mV), and high drug incorporation (93.1 ± 0.04%). Fourier Transform Infrared Spectroscopy (FTIR) analysis showed no chemical interaction between Atorvastatin and the lipid mixture. Differential Scanning Calorimetry (DSC) analysis of the AT-NLCs suggested the transformation of Atorvastatin crystal into an amorphous state. Administration of the optimized AT-NLCs led to a significant reduction (p &lt, 0.001) in serum levels of rats’ total cholesterol, triglycerides, and low-density lipoproteins. This change was histologically validated by reducing the relevant steatosis of the liver.

The purpose was to develop, optimize and assess Self-nanoemulsifying drug delivery system (SNEDDS) to enhance solubility and dissolution rate of the poorly-water soluble Atorvastatin/Ezetimibe (ATV/EZT) combination. The drugs solubility in various excipients was investigated and the combination showed the widest emulsifying region was determined using pseudo ternary phase diagram. Loaded SNEDDS were optimized using Design expert software®, and then investigated for thermodynamic stability, self-emulsification efficiency, cloud point, zeta potential, emulsion nature, loading capacity (LC) and encapsulation efficiency (EE), morphological characteristics and in-vitro release kinetics. The optimized formula dispersed spontaneously forming a thermodynamically stable aqueous nanoemulsion upon dilution with a globule size of 101.3 ± 0.47 nm. Cloud point (80–85 °C) and zeta potential of (−23 mV) indicate nanoemulsion formation at physiological temperature with no chance of separation and low aggregation possibility. Transmission electron microscope image showed nano spherical globules. According to In-vitro release studies, optimized formula showed improved dissolution rate with biphasic pattern where, the burst release phase showed first order kinetic and the gradual release phase showed Korsmeyer–Peppas release kinetic for both drugs. Improved oral bioavailability and greater ability to control serum cholesterol levels using ATV/EZT loaded L-SNEDDs compared to pure drugs suspension were demonstrated through in-vivo studies. SNEEDS were confirmed as a promising approach for enhancing the solubility and dissolution rate of lipophilic ATV/EZT combination compared to pure drugs and marketed product.

A factorial design (23) was applied to the formulation of rapid orally disintegrating tablets, in order to investigate the feasibility of using superdisintegrant and sublimation technique on the onset of antihypertensive action of captopril. The three independent factors, superdisintegrant (Ac-di-sol) concentration (2.5% or 5%), subliming agent type (menthol or camphor) and its concentration (5% or 10%), were studied for their main effects on three dependent responses, tablet hardness, disintegration time and in vitro drug release. Statistical analysis of obtained data and optimization of formulation variables were carried out using Design-Expert® software, which selected formulation (F10), prepared with 5% Ac-di-sol and 10% camphor, that displayed suitable in range hardness (3.425 ± 0.12 Kilopond), least disintegration time (17.48 ± 1.36 Seconds) and highest in vitro drug release (99.51 ± 0.24% after 8 min), as the optimum formulation with the highest desirability (0.937). F10 was then chosen for drug-excipients interaction studies (DSC and FTIR), accelerated stability study at 40 °C and 75% RH for 3 months and in vivo evaluation against conventional captopril tablets, in hypertensive rats, using tail-cuff method. F10 showed no interaction between drug and excipients, chemical and physical stability and 15 min faster normalization of mean arterial pressure, of hypertensive rats, than conventional captopril tablets.

In the pharmaceutical industry, the systematic optimization of formulation using Quality by Design (QbD) approach is economic, highly precise and ensures product quality. The current endeavor was aimed to prepare escitalopram ultra-fast melting tablets (UFMTs) based on QbD approach using suspension spray-coating technique. The (32) full factorial design was applied to obtain the optimal formulation in terms of; mannitol level (X1) and partially pre-gelatinized starch level (PPGS; X2) as independent formulation variables. The D-mannitol in certain formulations was spray-coated with a suspension of PPGS and granulated with distilled water (without PPGS) in other formulations using a fluid-bed granulator, producing granules compressed into tablets. The prepared tablets were tested for their mechanical strength, in-vitro and in-vivo disintegration, drug dissolution and in-vivo pharmacokinetic analysis using New Zealand rabbits. Results showed that the prepared tablets were tolerated with the USP criteria. Besides, ANOVA analysis demonstrated that X1 and X2 had a significant effect (P ≤ 0.05) on the dependent responses. Further, the developed tablets showed a good in-vitro/in-vivo correlation (R2 = 0.9953) in the disintegration time. Moreover, analysis of pharmacokinetic parameters suggested that optimized escitalopram UFMTs might have pharmaceutical bioequivalence to the marketed product. Finally, QbD considered an efficient paradigm for product optimization.

Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYL(TM) T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level.

Objective: This study aims to develop controlled release buccal tablets of losartan potassium based on bioadhesion using direct compression technique. Materials and Methods: The bioadhesive buccal tablets of losartan potassium were prepared after preliminary drug-excipients compatibility studies and micromeretics study for powder blends. The tablets were prepared by direct compression utilizing carbopol 934LR as a primary bioadhesive polymer either with or without chitosan or hydroxypropyl methylcellulose E15LV as secondary polymers. Other excipients included PVP K30 as a binder, magnesium stearate as a lubricant and mannitol as a diluent. The tablets were evaluated for weight variation, thickness and diameter, hardness, friability, drug content, surface pH, Ex-vivo residence time and bioadhesion force, In-vitro swelling and drug release study. The analysis of the release profiles in the light of distinct kinetic models (zero order, first order, Higuchi, Hixson-Crowell and Korsmeyer–Peppas) was carried out. Results and Discussion: The formula containing 40% w/w bioadhesive polymers of carbopol 934LR and chitosan (1:2) was selected as the optimum one based on a ranking methodology and then, it was subjected to Ex-vivo permeation and physical stability study in human saliva. Swelling index was 78.32±1.84% after 7h and tablets showed a neutral surface pH. Ex-vivo residence time was long enough for more than 10h. Ex-vivo bioadhesion force was 0.38±0.01N. Drug release was 57.64±3.43% after 8h following zero order kinetics with a steady state permeation flux of 0.959mg/cm2h. Tablets were physically stable in human saliva. Conclusion: These formulae improved, controlled and prolonged the release of losartan potassium from a buccal bioadhesive system for at least 8h in a simple way which can achieve a high patient compliance.

Aims: The aim of this study was to explore the practicability of preparation of solid lipid nanoparticles of Glyceryl monostearate containing Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide as model drugs. The physicochemical properties of the prepared formulae like particle size, drug entrapment efficiency, drug loading capacity, yield content and in-vitro drug release behavior were also measured. Methodology: Solid lipid nanoparticles loaded with three model lipophilic drugs were prepared by high shear hot homogenization method. The model drugs used are Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide. Glyceryl monostearate was used as lipid core; Tween 20 and Tween 80 were employed as surfactants and lecithin as co-surfactant. Many formulation parameters were controlled to obtain high quality nanoparticles. The prepared solid lipid nanoparticles were evaluated by different standard physical and imaging methods. The efficiency of drug release form prepared formulae was studied using in vitro technique with utilize of dialysis bag technique. The stability of prepared formulae was studied by thermal procedures and infrared spectroscopy. Results: The mean particle diameter measured by laser diffraction technique was (194.6±5.03 to 406.6±15.2 nm) for Dibenzoyl peroxide loaded solid lipid nanoparticles, (220±6.2 to 328.34±2.5) nm for Erythromycin loaded solid lipid nanoparticles and (227.3±2.5 to 480.6±24) nm for Triamcinolone acetonide loaded solid lipid nanoparticles. The entrapment efficiency and drug loading capacity, determined with ultraviolet spectroscopy, were 80.5±9.45% and 0.805±0.093%, for Dibenzoyl peroxide, 96±11.5 and 0.96±0.012 for Triamcinolone acetonide and 94.6±14.9 and 0.946±0.012 for Erythromycin base respectively. It was found that model drugs showed significant faster release patterns when compared with commercially available formulations and pure drugs (pE‚0.05). Thermal analysis of prepared solid lipid nanoparticles gave indication of solubilization of drugs within lipid matrix. Fourier Transformation Infrared Spectroscopy (FTIR) showed the absence of new bands for loaded solid lipid nanoparticles indicating no interaction between drugs and lipid matrix and being only dissolved in it. Electron microscope of scanning and transmission techniques indicated sphere form of prepared solid lipid nanoparticles with smooth surface with size below 100 nm. Conclusions: Solid lipid nanoparticles with small particle size have high encapsulation efficiency, and relatively high loading capacity for Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide as model drugs can be obtained by this method.

Aims: 1) To study the effect of some formulation variables on drug load, encapsulation efficiency, swelling ratio, mucoadhesion and drug release. 2) Optimize the mucoadhesion capabilities for targeting drug absorption and releasecontrolling capabilities of algi nate beads. Methodology: Alginatebeads were prepared by dripping sodium alginate gel into calcium chloride solution and then dried overnight at ambient temperature. The effects of alginate concentration, cross linker concentration, cross linking time, vol