Rakesh P. Patel

Formulation and evaluation of mucoadhesive glipizide microspheres.

The purpose of this research was to formulate and system-atically evaluate in vitro and in vivo performances of mucoadhesive microspheres of glipizide. Glipizide microspheres containing chitosan were prepared by simple emulsification phase separation technique using glutaraldehyde as a cross-linking agent. Results of preliminary trials indicate that volume of cross-linking agent, time for cross-linking, polymer-to-drug ratio, and speed of rotation affected characteristics of microspheres. Microspheres were discrete, spherical, and free flowing. The microspheres exhibited good mucoadhesive property in the in vitro wash-off test and also showed a high percentage drug entrapment efficiency. A 32 full factorial design was employed to study the effect of independent variables, polymer-to-drug ratio (X1), and stirring speed (X2) on dependent variables percentage mucoadhesion, t80, drug entrapment efficiency, and swelling index. The best batch exhibited a high drug entrapment efficiency of 75% and a swelling index of 1.42; percentage mucoadhesion after 1 hour was 78%. The drug release was also sustained for more than 12 hours. The polymer-to-drug ratio had a more significant effect on the dependent variables. In vivo testing of the mucoadhesive microspheres to albino Wistar rats demonstrated significant hypoglycemic effect of glipizide.

Physicochemical Characterization and Dissolution Study of Solid Dispersions of Lovastatin with Polyethylene Glycol 4000 and Polyvinylpyrrolidone K30

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, Lovastatin, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K30 (PVP K30) in different drug-to‐carrier ratios. Dispersions with PEG 4000 were prepared by fusion-cooling and solvent evaporation, whereas dispersions containing PVP K30 were prepared by solvent evaporation technique. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, X-ray powder diffraction, and FT-IR spectroscopy. The aqueous solubility of Lovastatin was favored by the presence of both polymers. The negative values of the Gibbs free energy and enthalpy of transfer explained the spontaneous transfer from pure water to the aqueous polymer environment. Solid-state characterization indicated Lovastatin was present as amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure Lovastatin, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersion prepared with PVP showed the highest improvement in wettability and dissolution rate of Lovastatin. Even physical mixture of Lovastatin prepared with both polymers also showed better dissolution profile than that of pure Lovastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile of Lovastatin compared with tablets containing Lovastatin without PEG or PVP.

Formulation and evaluation of curcumin gel for topical application.

The aim of the present investigation was to develop and study topical gel delivery of curcumin for its anti-inflammatory effects. Carbopol 934P (CRB) and hydroxypropylcellulose (HPC) were used for the preparation of gels. The penetration enhancing effect of menthol (0–12.5% w/w) on the percutaneous flux of curcumin through the excised rat epidermis from 2% w/w CRB and HPC gel system was investigated. All the prepared gel formulations were evaluated for various properties such as compatibility, drug content, viscosity, in vitro skin permeation, and anti-inflammatory effect. The drug and polymers compatibility was confirmed by Differential scanning calorimetry and infrared spectroscopy. The percutaneous flux and enhancement ratio of curcumin across rat epidermis was enhanced markedly by the addition of menthol to both types of gel formulations. Both types of developed topical gel formulations were free of skin irritation. In anti-inflammatory studies done by carrageenan induced rat paw oedema method in wistar albino rats, anti-inflammatory effect of CRB, HPC and standard gel formulations were significantly different from control group (P < 0.05) whereas this effect was not significantly different for CRB and HPC gels formulations to that of standard (diclofenac gel) formulation (P > 0.05). CRB gel showed better % inhibition of inflammation as compared to HPC gel.

Design and evaluation of transdermal drug delivery system for curcumin as an anti-inflammatory drug.

The purpose of this research was to develop a matrix-type transdermal therapeutic system containing herbal drug, curcumin (CUR), with different ratios of hydrophilic (hydroxyl propyl methyl cellulose K4M [HPMC K4M]) and hydrophobic (ethyl cellulose [EC]) polymeric systems by the solvent evaporation technique. Different concentrations of oleic acid (OA) were used to enhance the transdermal permeation of CUR. The physicochemical compatibility of the drug and the polymers was also studied by differential scanning calorimetry (DSC) and infrared (IR) spectroscopy. The results suggested no physicochemical incompatibility between the drug and the polymers. Formulated transdermal films were physically evaluated with regard to drug content, tensile strength, folding endurance, thickness, and weight variation. All prepared formulations indicated good physical stability. In vitro permeation studies of formulations were performed by using Franz diffusion cells. The results followed Higuchi kinetics, and the mechanism of release was diffusion-mediated. Formulation prepared with hydrophilic polymer containing permeation enhancer showed best in vitro skin permeation through rat skin as compared with all other formulations. This formulation demonstrated good anti-inflammatory activity against carrageenan-induced oedema in Wistar albino rats similar to standard formulation.

Preparation, Characterization, and Dissolution Behavior of a Solid Dispersion of Simvastatin with Polyethylene Glycol 4000 and Polyvinylpyrrolidone K30

The aim of the present study was to improve the solubility and dissolution rate of a poorly water‐soluble drug, Simvastatin, by a solid dispersion technique. Solid dispersions were prepared with polyethylene glycol 4000 (PEG 4000) by fusion‐cooling and solvent evaporation techniques whereas with polyvinylpyrrolidone K30 (PVP K30) by solvent evaporation technique in different drug‐to‐carrier ratios. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, x‐ray powder diffraction, and FTIR spectroscopy. The aqueous solubility of Simvastatin was favored by the presence of both polymers. Solid state characterization indicated Simvastatin was present as amorphous material and entrapped in polymer matrix. Solid dispersion prepared with PVP showed highest improvement in wettability and dissolution rate of Simvastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile of Simvastatin as compared to tablet containing Simvastatin without PEG or PVP.

Formulation, Characterization, and Optimization of Fast-Dissolve Tablets Containing Celecoxib Solid Dispersion

Celecoxib is a poorly water-soluble drug, and bioavailability from its crystalline form is very low. The purpose of the present investigation was to increase the solubility and dissolution rate of celecoxib by preparing a solid dispersion with polyvinyl pyrrolidone K30 (PVP-K30) using a solvent-evaporation method. The dissolution profiles of developed formulations in distilled water containing 1% SLS were studied. Drug–polymer interactions were investigated using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). For the preparation of celecoxib fast-dissolve tablets, a 1:2 solid dispersion with PVP-K30 was used with croscarmellose sodium as a superdisintegrant and Pearlitol 200SD (pearlitol) as a pore-forming agent. A 3 2 full-factorial design was employed to study the effect of independent variables, the amounts of croscarmellose sodium (X1) and pearlitol (X2), on dependent variables, disintegration time, percentage friability, wettability, and percentage of drug released after 20 min (Q20). The results show that a dispersion of the drug in polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio is the controlling factor for dissolution improvement. FTIR spectra show no chemical incompatibility between the drug and PVP-K30. FTIR and DSC data indicate that celecoxib was in the amorphous form, which explains the faster dissolution rate of the drug from its solid dispersions. Concerning the optimization study, multiple regression analysis reveals that an optimum concentration of croscarmellose sodium and a higher percentage of pearlitol are required for obtaining rapidly disintegrating tablets.

Physico-Chemical Characterization and In Vitro Dissolution Assessment of Clonazepam—Cyclodextrins Inclusion Compounds

The objectives of this research were to prepare and characterize inclusion complexes of clonazepam with β-cyclodextrin and hydroxypropyl-β-cyclodextrin and to study the effect of complexation on the dissolution rate of clonazepam, a water-insoluble lipid-lowering drug. The phase-solubility profiles with both cyclodextrins were classified as AP-type, indicating the formation of 2:1 stoichiometric inclusion complexes. Gibbs free energy

Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique

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