Formulation development and evaluation of nifedipine as pylorospasm inhibitor.

INTRODUCTION: In this study, different nifedipine-loaded formulations were prepared to treat pylorospasm, a sphincter muscle disorder characterized by delayed gastric emptying process. The efficacy of formulation was evaluated in patients by subjective assessment, gamma scintigraphic approaches, and confocal microscopy. METHODS: Nifedipine-loaded different formulations such as sucrose bead, pellets, and microparticles (slugging method, ionotropic gelation, and chemical denaturation) were designed. The studies were performed on 50 subjects, of which 30 subjects were treated with optimized nifedipine loaded microcapsules while 20 subjects were given capsule becosule-Z as a control. The efficacy of formulation was assessed by comparing symptoms like dyspepsia, abdominal pain, abdominal fullness, poor appetite, nausea, vomiting, and irregular motion. The effectiveness of formulation was also assessed by gamma scintigraphic studies by determining the rate of emptying of a radioactivity labeled standard meal from patients' stomach into the duodenum. Confocal microscopy was used to assess targeting potential of developed formulation. RESULTS: Drug-loaded alginate-chitosan microcapsules were found to be satisfactory, in terms of controlled drug release, surface morphology, and bioadhesive properties and thus selected for in vivo studies. Clinical studies revealed the efficacy of formulation in abolishing various GI symptoms at high altitude. Associated symptoms such as dyspepsia, abdominal pain, poor appetite, nausea, vomiting, and irregular motion were recovered by 75, 62, 76.5, 86.7, 85.7, and 37.5%, respectively in nifedipine-treated patients. In comparison, 73.7, 40, 33.3, 40, 20, and 0% recoveries were observed in patients given control treatment only. Gamma Scintigraphic studies in lab also revealed 2.425 ± 0.245 (p < .05) times improvement in gastric emptying rate in patients with diabetic gastroparesis. Confocal analysis showed better targeting and penetration in pyloric region when formulation was administered in form of high-density microcapsules. CONCLUSIONS: Results strongly suggest that nifedipine loaded mucoadhesive formulation has a targeting potential which accelerates gastric emptying process in gastroparesis patients, and thus the formulation might prove useful as a potent prokinetic agent.

Optimisation of polyherbal gels for vaginal drug delivery by Box-Behnken statistical design.

The present research work aimed at development and optimisation of mucoadhesive polyherbal gels (MPG) for vaginal drug delivery. As the rheological and mucoadhesive properties of the gels correlate well to each other the prepared MPGs were optimised for maximum mucoadhesion using a relationship between the storage modulus (G') and Gel Index (GI), by employing a 3-factor, 3-level Box-Behnken statistical design. Independent variables studied were the polymer concentration (X(1)), honey concentration (X(2)) and aerosil concentration (X(3)). Aerosil has been investigated for the first time to improve the consistency of gels. The dependent variables studied were the elastic modulus, G'(Y(1)), gel index (Y(2)), and maximum detachment force (Y(3)) with applied constraints of 500

Validated high-performance thin-layer chromatography method for determination of trigonelline in herbal extract and pharmaceutical dosage form.

A new, simple, sensitive, selective, precise and robust high-performance thin-layer chromatographic (HPTLC) method for analysis of trigonelline was developed and validated for the determination of trigonelline in herbal extracts and in pharmaceutical dosage forms. Analysis of trigonelline was performed on TLC aluminium plates pre-coated with silica gel 60F-254 as the stationary phase. Linear ascending development was carried out in twin trough glass chamber saturated with mobile phase consisting of n-propanol-methanol-water (4:1:4, v/v/v) at room temperature (25+/-2 degrees C). Camag TLC scanner III was used for spectrodensitometric scanning and analysis in absorbance mode at 269 nm. The system was found to give compact spots for trigonelline (R(f) value of 0.46+/-0.02). The linear regression analysis data for the calibration plots showed good linear relationship with r2=0.9991+/-0.0002 in the concentration range 100-1200 ng spot(-1) with respect to peak area. According to the International Conference on Harmonization (ICH) guidelines the method was validated for precision, recovery, robustness and ruggedness. The limits of detection and quantification were determined. The trigonelline content of herbal extracts quantified and estimated from the formulation was found to be well within limits (+/-5% of the labeled content of the formulations). Statistical analysis of the data showed that the method is reproducible and selective for the estimation of trigonelline.