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Th accurate rapid, simple and selective reversed phase high performance liquid chromatography (RP-HPLC) has been established and validated for the determination of captopril (CAP). Chromatographic separation was accomplished using prepacked ODSI C18 column (250 mm × 4.6 mm with 5 μm particle size) in isocratic mode, with mobile phase consisting of water: acetonitrile (60:40 v/v), pH adjusted to 2.5 by using 85% orthophosphoric acid at a flow rate of 1 mL/min and UV detection was performed at 203 nm. RP-HPLC method used for the analysis of CAP in mobile phase and rabbit plasma was established and validated as per ICH-guidelines. It was carried out on a well-defined chromatographic peak of CAP was established with a retention time of 4.9 min and tailing factor of 1.871. The liquid–liquid extraction method was used for extraction of CAP from the plasma. Excellent linearity (R2 = 0.999) was shown over range 3.125–100 µg/mL with mean percentage recoveries ranges from 97 to 100.6%. Parameters of precision and accuracy of the developed method meet the established criteria. Intra and inter-day precision (% relative standard deviation) study was also performed which was less than 2% which indicate good reproducibility of the method. The limit of detection (LOD) and quantification for the CAP in plasma were 3.10 and 9.13 ng/mL respectively. The method was suitably validated and successfully applied to the determination of CAP in rabbit plasma samples.

Enteric coating of hydrogel beads is an effective approach to resolve the drug entrapment problem reported in previous studies. In the present study, microencapsulation of drug in hydrogel beads with extrusion-dripping technique was used for the improvement of the drug entrapment efficiency. Calcium chloride dehydrate was used as a cross-linking agent and oil-in-oil solution of eudragit S-100 was used as coating material while diclofenac sodium was used as a model drug. Optical microscopy, scanning electron microscopy, weight, elemental, and size variation of prepared hydrogels beads were analyzed and found within the acceptable limits. The drug loading and release studies of the coated beads were evaluated. Retardation of the model drug in gastric and intestinal pH environment until 8 h was observed which made the prepared hydrogels more targeted and colon-specific. In acidic pH 1.2, negligible percentage release was observed, whereas at pH 7.4, 98% diclofenac sodium was estimated after 8 h. In vitro release, kinetic studies proved that concentration-dependent release behavior of diclofenac sodium followed Fick’s law of diffusion in coated form, while non-Fickian behavior was observed in uncoated beads. Prepared hydrogel beads may be used as a promising tool for sustained release of drug targeting colon.

The aim of present research aims to fabricate a system of enteric coating of hydrogel beads with pH-sensitive polymer, which shows solubility at pH > 7, and explore their potential to target the colon for drug delivery. Hydrogel beads were fabricated through the extrusion-dripping technique followed by ion gelation crosslinking. Moreover, freeze-thaw cycle was implemented for crosslinking of polyvinyl alcohol (PVA)/Ca-alginate blend beads. The oil-in-oil solvent evaporation method was adopted for the Eudragit coating of hydrogel beads using different coat: core ratios (4:1 or 8:1). Coated and uncoated hydrogel beads were evaluated by in vitro physicochemical properties, swelling and drug release behaviours, and in vivo pharmacokinetics, swelling, and toxicity evaluation. Diclofenac sodium was loaded as an experimental drug. Drug entrapment efficiency for the PVA/Ca-alginate beads was calculated as 98%, and for Ca-alginate beads, it came out to a maximum of 74%. Drug release study at various pH suggested that, unlike uncoated hydrogel beads, the coated beads delay the release of diclofenac sodium in low pH of the gastric and intestinal environment, thus targeting the colon for the drug release. It was concluded that Eudragit S-100-coated hydrogel beads could serve as a more promising and reliable way to target the colon for drug delivery. Graphical abstract

Water insoluble drugs with a short plasma half-life face the pharmacokinetic (PK) barriers of low oral absorption from the gastrointestinal route of drug administration and rapid clearance from systemic circulation. We report the synthesis and pharmaceutical profiling of a hybrid dosage form consisting of hydrophilic polymer encapsulated nanoparticles (NPs) of a hydrophobic drug, compressed inside tablets and optimized for efficient PK oral delivery. Four different polymers, i.e. hydroxypropylmethyl cellulose, Na-alginate, pectin and polyvinylpyrrolidone were used separately to nano-encapsulate (700 nm to 1 μm diameter) lornoxicam, a model hydrophobic drug with a short PK half-life, by a solvent emulsification method. The prepared NPs were compressed directly into tablets. The PK study in rats revealed improved oral bioavailability and better PK parameters of the drug after the oral administration of NPs carrying (NC) tablets for each polymer. The same was observed for the pharmacological activity in terms of carrageenan-induced inflammation in rat paw. In the in vitro drug release study, the NC tablets provided additional control over drug release by an interaction of the surface polymer of NPs with the tablet's matrix polymer. NPs showed better rheological properties as compared to crystalline drug, enabling efficient flow and processing of NPs in the tableting machine. The NC tablets appeared advantageous compared to conventional crystalline lornoxicam carrying (CL) tablets, conventional market tablets or even nanoparticles alone in terms of the ease of administration, improved drug stability, tunable drug release and enhanced oral bioavailability.

In the present study pH-sensitive polyvinylpyrrolidone/acrylic acid (PVP/AA) hydrogels were synthesized by free radical polymerization in the presence of ethylene glycol dimethacrylate (EGDMA) as a cross-linker. For this purpose, different concentrations of PVP, AA and EGDMA were used to synthesize polymeric networks. This study focused on evaluating the effect of the composition on the swelling of hydrogels and release of tramadol hydrochloride at varying pH (1.2, 5.5, 6.5 and 7.5). Gel fraction, porosity and diffusion coefficient were also determined. The hydrogels were characterized using scanning electron microscopy for surface morphology, Fourier transform infrared spectroscopy and X-ray diffraction for studying possible chemical interactions. The hydrogels exhibited a pH-dependent swelling behavior. The degree of swelling, as well as drug release from PVP/AA hydrogel, was significantly increased as pH varied from 1.2 to 7.5. Swelling was increased by increasing the AA content, while a decrease in sw...

Flurbiprofen loaded PCL/PVP blend microspheres were prepared by o/w solvent evaporation method using various concentrations of gelatin as emulsifying agent. Microsphere recovery decreased with a decrease in the concentration of the emulsifier in the dispersion. Encapsulation efficiency and drug loading of microspheres increased with decrease in concentration of emulsifying agent. Hydration rate, encapsulation efficiency and drug loading of microspheres increased with increase in concentration of PVP. Rheological properties showed free flowing nature of microspheres. SEM (Scanning electron microscope) revealed microspheres were discrete, spherical and became porous with decrease in concentration of emulsifying agent but smooth with higher concentration of emulsifying agent. FTIR (Fourier transform infrared spectroscopy) spectra of pure and encapsulated flurbiprofen in all formulation showed no significant difference in characteristic peaks, suggesting stability of flurbiprofen during encapsulation process. X-RD (X-ray powder diffractometry) of pure flurbiprofen shows sharp peaks, which decreases on encapsulation, indicating dispersion at molecular level and hence decrease in the crystallinity of drug in microspheres. Microspheres showed an enteric nature at pH 1.2 and a sustained release pattern at pH 6.8. Rapid drug release was observed in microspheres with higher concentration of PVP (polyvinylpyrrolidone), PVP acts as channeling agent. Formulation with low concentration of emulsifying agent also showed a fast release due to porous structure. Drug release kinetics followed zero order at pH 1.2 while at pH 6.8 Higuchi model was best fitted and was found non fickian.

In the present work crosslinked methyl methacrylate-co-itaconic acid (MMA-co-IA) hydrogels were prepared by free radical copolymerization of methyl methacrylate (MMA) with itaconic acid (IA) using ethylene glycol dimethacrylate (EGDMA) and N, N methylene bisacrylamide (MBAAm) as crosslinkers and benzoyl peroxide as initiator. Prepared hydrogels were investigated for dynamic and equilibrium swelling studies. For swelling behaviour, effect of pH, monomeric compositions, degree of crosslinking and type of crosslinking agent were investigated. Swelling studies were performed in the USP phosphate buffer solutions of varying pH 1.2, 4.5, 5.5, 6.5 and 7.0. Results showed that swelling increased by increasing IA content in hydrogels structure. This may be due to the presence of more carboxylic groups available for ionization. Swelling was decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Hydrogels were characterized by Fourier transform infrared (FTIR), and scanning electron microscope (SEM). Polymer-solvent interaction parameters (χ) of hydrogels were determined by using Flory–Rehner theory of equilibrium swelling values. The analysis of diffusion mechanism from gels using Peppas model showed that all monomeric compositions and degrees of crosslinking followed Fickian diffusion.

Background The present work objective was to prepare and to observe the effect of ethylene glycol dimethacrylate on swelling and on drug release behavior of pH-sensitive acrylic acid–polyvinyl alcohol hydrogel. Methods In the present work, pH sensitive acrylic acid–polyvinyl alcohol hydrogels have been prepared by free radical polymerization technique in the presence of benzoyl peroxide as an initiator. Different crosslinker contents were used to observe its effect on swelling and on drug release. Dynamic and equilibrium swelling studies of prepared hydrogels were investigated in USP phosphate buffer solutions of pH 1.2, 5.5, 6.5 and 7.5 with constant ionic strengths. Hydrogels were evaluated for polymer volume fraction, solvent interaction parameter, molecular weight between crosslinks, number of links per polymer chain, diffusion coefficient, sol–gel fraction and porosity. To demonstrate the release pattern of the drug, zero-order, first-order, higuchi and korsmeyer-peppas models were applied. Quality and consistency of hydrogels was examined by FTIR and surface morphology of hydrogels was examined by SEM. Results Decrease in swelling and in drug release was seen by increasing content of ethylene glycol dimethacrylate. A remarkable high swelling was observed at high pH indicating the potential of this hydrogel for delivery of drugs to intestine. By increasing the concentration of ethylene glycol dimethacrylate, porosity decreased. Order of release was observed first order in all cases and the mechanism was non–fickian diffusion. FTIR confirmed the formation of network. SEM results showed the incorporation of drug. Conclusion The prepared hydrogels can be suitably used for targeted drug delivery to the intestine.

Flurbiprofen is a potent non-steroidal anti-inflammatory drug, prescribed commonly for musculoskeletal and joint disorders like arthritis. It is well established that drug degradation during storage and transportation is of particular issue in tropical countries like Pakistan, having areas with temperature variations from 0 o C (Muree, Islamabad, Sawat and Azad Jammu Kashmir) to 50 o C (Sibi, Jackababad, Nawabshah, Larkana, Multan and Bahawalpur) and some areas with high relative humidity (Karachi). Present study was designed to evaluate five different national brands of flurbiprofen 100 mg film coated tablets by accelerated stability studies and examined for the parameters of hardness, disintegration, dissolution and assay for drug concentration in formulation after one, three and six months duration at controlled tropical conditions of temperature and relative humidity. Dosage forms of all selected national brands were found stable even after expiry date.

We report synthesis, characterization, and drug release attributes of a series of novel pH-sensitive poly(acrylic-co-vinylsulfonic) acid hydrogels. These hydrogels were prepared by employing free radical polymerization using ethylene glycol dimethacrylate (EGDMA) and benzyl peroxide (BPO) as cross-linker and initiator, respectively. Effect of acrylic acid (AA), polyvinylsulfonic acid (PVSA), and EGDMA on prepared hydrogels was investigated. All formulations showed higher swelling at high pHs and vice versa. Formulations containing higher content of AA and EGDMA show reduced swelling, but one with higher content of PVSA showed increased swelling. Hydrogel network was characterized by determining structural parameters and loaded with isosorbide mononitrate. FTIR confirmed absence of drug polymer interaction while DSC and TGA demonstrated molecular dispersion of drug in a thermally stable polymeric network. All the hydrogel formulations exhibited a pH dependent release of isosorbide mononitrate which was found to be directly proportional to pH of the medium and PVSA content and inversely proportional to the AA contents. Drug release data were fitted to various kinetics models. Results indicated that release of isosorbide mononitrate from poly(AA-co-VSA) hydrogels was non-Fickian and that the mechanism was diffusion-controlled.

Solid dispersions of artemether (ARM), a poorly soluble drug, were prepared using polyvinylpyrrolidone (PVPK25, MW 25000) and polyethyleneglycol (PEG4000, MW 4000) as excipients. These dispersions were studied by physical mixture, freeze-drying, and melting methods. They were characterized by X-ray diffraction pattern, fourier transform infrared spectrophotometry, differential scanning calorimetery, and dissolution studies. X-ray diffraction pattern revealed the complete crystalline nature of artemether, whereas physical mixtures, melt mixtures (MM), and freeze-dried solid dispersions (FDSD) of ARM-PVP and ARM-PEG showed reduced peak intensities with increased PVP/PEG content. PEG showed lower decreases in intensity than PVP preparations. Differential scanning calorimetery also confirmed this finding by showing either a small or absent endotherm. Red shifts in O-H stretching vibrations of ARM were higher in the MM of ARM-PVP than its FDSD as exhibited by fourier transform infrared spectrophotometry. The carbonyl peak of PEG was blue shifted in MM and FDSD, whereas the C=O peak of PVP was red shifted in FDSD and MM, indicating different H-bonding by PEG and PVP with ARM. The rate of dissolution (phosphate buffer at pH 4.5) was improved up to 4-fold in MM and FDSD compared to artemether, and up to 50% compared to physical mixtures. The preparation of solid dispersions influenced the rate of dissolution at various drug-carrier ratios, i.e., the dissolution order of 1:1-1:4 ratio was MM > FDSD; FDSD > MM at 1:6-1:8 ratios of both ARM-PVP and ARM-PEG; and FDSD of ARM-PEG > FDSD of ARM-PVP > MM of ARM-PEG > MM of ARM-PVP at a 1:10 ratio.