Improvement in photostability of pantoprazole sodium by microencapsulation.

Pantoprazole sodium is a proton pump inhibitor used to treat peptic ulcers and gastroesophageal reflux. This drug is unstable in acid solution, in the presence of salts, as well as in UVC radiation. Hence the aim of present study was to develop microparticles that will protect the drug from degradation in gastric acid and increase its photostability. Microparticles were prepared by the solvent evaporation method using Eudragit S 100 as enteric polymer by varying drug: polymer ratios ranging from 1:1 to 1:4. The developed microparticles were characterized for surface morphology, particle size, encapsulation efficiency, and stability in acidic media. Microparticles obtained with the ratio 1:4 were spherical, had a smooth surface, and showed the highest percent entrapment of 67 ± 2.1%. Microparticles showed uniform size distribution; about 87% of microparticles were in the size range of 50 to 75 µm. In vitro dissolution studies showed no drug release in acidic media; further prolonged drug release for a period of 9 h was obtained with a 1:4 in phosphate buffer pH 7.4 following Higuchi release kinetics with regression value of 0.9896. Photodegradation studies were performed in solar light and in UV light at 254 nm and 366 nm for 7 days. The concentration of drug was determined spectrophotometrically at 290 nm. Percent degradation under solar light for pure drug was 25%, and no significant degradation was seen in drug-loaded microparticles. Degradation under UV radiation 254 nm and 366 nm was found to be 38.6% and 12.11% and 35.11% and 6.13% for pure drug and drug-loaded microparticles respectively. LAY ABSTRACT: Pantoprazole sodium is widely used in treatment of acid-related disorders and management of gastroesophageal reflux diseases. It is an acid-labile drug that degrades in the stomach at pH 1-2 and is highly unstable in UVC light. Hence the aim of research work was to improve photostability of pantoprazole and protect it from the acidic environment by loading in gastroresistant microparticles. Various batches of microparticles were prepared by the solvent evaporation method using Eudragit S 100 as an enteric polymer that solubilizes at pH 7. Developed microparticles were characterized for different parameters and the formulation showing the highest drug entrapment was selected for photodegradation studies. Photodegradation studies were performed in solar light and in UV light at 254 nm and 366 nm for 7 days. The concentration of drug was determined spectrophotometrically at 290 nm. The percent degradation under solar light for pure drug was 25% and no significant degradation was seen in drug-loaded microparticles. Degradation under UV radiation 254 nm and 366 nm was found to be 38.6% and 12.11% and 35.11% and 6.13% for pure drug and drug-loaded microparticles, respectively. Microencapsulation decreases the penetration as well as absorption of radiation, which enhances the protection of pantoprazole sodium.

Ungual and transungual drug delivery.

Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate.

Passive and iontophoretic permeation of glipizide.

In vitro iontophoretic delivery of glipizide across the pigskin was investigated. The experiment was carried out at three different donor drug concentrations using cathodal iontophoresis (current density 0.5 mA cm(-2)) with corresponding passive controls. At all concentration levels, iontophoresis showed enhanced permeation rate compared to passive controls (P<0.01). For passive permeation, the steady-state flux significantly increased with the increase in donor drug concentration (P<0.01). Passive process followed zero-order profile while the profile was nonlinear in iontophoresis. Competition by chloride ions released in the cathode compartment could be the reason. Flux enhancement was highest at the lowest drug load and lowest at the highest drug load. The target flux of glipizide was calculated to be 0. 4147 micromol h(-1). As the highest flux obtained was 0.2727 micromol cm(-2) h(-1), it can be said that glipizide is a promising candidate for iontophoretic delivery.

Design and optimization of diclofenac sodium controlled release solid dispersions by response surface methodology.

A 3(2) factorial design was employed to produce controlled release solid dispersions of diclofenac sodium in Eudragit RS and RL by coevaporation of their ethanol solution in a flash evaporator. The effect of critical formulation variables namely total polymer pay loads and levels of Eudragit RL on percent drug incorporation (% DI), drug release at the end of 12 hours (Rel(12)) and drug release at the end of 3 hours (Rel(3)) were analyzed using response surface methodology. The parameters were evaluated using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis and analysis of variance. Both the formulation variables studied exerted a significant influence (p < 0.05) on the drug release whereas the total polymer levels emerged as a lone factor significantly influencing the percent drug incorporation. Numerical optimization technique employing desirability approach was used to develop a new formulation by setting constraints on the dependent and independent variables. The experimental values of % DI, Rel(12) and Rel(3) for the optimized batch were found to be 95.22 +/- 1.13%, 74.52 +/- 3.16% and 29.37 +/- 1.26% respectively which were in close agreement with those predicted by the mathematical models. The Fourier transform infrared spectroscopy, Differential scanning calorimetry and Powder x-ray diffractometry confirmed that the drug was reduced to molecular or microcrystalline form in the hydrophobic polymeric matrices, which could be responsible for the controlled drug release from the solid dispersions. The drug release from the solid dispersions followed first order rate kinetics and was characterized by Higuchian diffusion model.

Formulation optimization of propranolol hydrochloride microcapsules employing central composite design.

A central composite design was employed to produce microcapsules of propranolol hydrochloride by o/o emulsion solvent evaporation technique using a mixture of cellulose acetate butyrate as coat material and span-80 as an emulsifier. The effect of formulation variables namely levels of cellulose acetate butyrate (X(1)) and percentage of Span-80 (X(2)) on encapsulation efficiency (Y(1)), drug release at the end of 1.5 h (Y(2)), 4 h (Y(3)), 8 h (Y(4)), 14 h (Y(5)), and 24 h (Y(6)) were evaluated using the F test. Mathematical models containing only the significant terms were generated for each response parameter using multiple linear regression analysis and analysis of variance. Both the formulation variables exerted a significant influence (P <0.05) on Y(1) whereas the cellulose acetate butyrate level emerged as the lone factor which significantly influenced the other response parameters. Numerical optimization using desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of Y(1), Y(2), Y(3), Y(4), Y(5), and Y(6) for the optimized formulation was found to be 92.86+/-1.56% w/w, 29.58+/-1.22%, 48.56+/-2.56%, 60.85+/-2.35%, 76.23+/-3.16% and 95.12+/-2.41%, respectively which were in close agreement with those predicted by the mathematical models. The drug release from microcapsules followed first order kinetics and was characterized by Higuchi diffusion model. The optimized microcapsule formulation developed was found to comply with the USP drug release test-1 for extended release propranolol hydrochloride capsules.

Influence of beta-cyclodextrin complexation on glipizide release from hydroxypropyl methylcellulose matrix tablets.

Glipizide was complexed with beta-cyclodextrin in an attempt to enhance the drug solubility. The phase solubility diagram was classified as A(L) type, which was characterized by an apparent 1:1 stability constant that had a value of 413.82 M(-1). Fourier transform infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry and proton nuclear magnetic resonance spectral analysis indicated considerable interaction between the drug and beta-cyclodextrin. A 2(3) factorial design was employed to prepare hydroxypropyl methylcellulose (HPMC) matrix tablets containing the drug or its complex. The effect of the total polymer loads (X1), levels of HPMC K100LV (X9), and complexation (X3) on release at first hour (Y1), 24 h (Y2), time taken for 50% release (Y3), and diffusion exponent (Y4) was systematically analyzed using the F test. Mathematical models containing only the significant terms (P < 0.05) were generated for each parameter by multiple linear regression analysis and analysis of variance. Complexation was found to exert a significant effect on Y1, Y2, and Y3, whereas total polymer loads significantly influenced all the responses. The models generated were validated by developing two new formulations with a combination of factors within the experimental domain. The experimental values of the response parameters were in close agreement with the predicted values, thereby proving-the validity of the generated mathematical models.