A unique formulation of sodium bicarbonate buffered pantoprazole powder for oral suspension: perspectives from an active controlled cross-over bioequivalence study

Background:The aim was determining bioequivalence between pantoprazole buffered powder for oral suspension and pantoprazole enteric coated tablets under fasting conditions in healthy volunteers.Methods:In randomized cross-over study, participants were administered a single oral dose of pantoprazole powder as suspension 40 mg (sodium bicarbonate as buffer) or one enteric coated tablet of pantoprazole 40 mg, with240�ml of water as per the randomization schedule in each study period. Blood samples were collected at pre-dose and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 14, 16and 24hours post-dose. Plasmaconcentration of pantoprazole was determined with LC-MS and various pharmacokinetic parameters like Cmax, AUC0-t, AUC0-inf were compared between test and reference groups.Results:Amongst 41 subjects, Cmax(3752.4�84.6 vs. 3521.7�99.5 ng/ml)was achieved higher in less Tmaxtime (1 (0.28) vs. 2.3 (0.83) hrs)with test drug as compared to reference drug. The ratios of geometric least square mean and its 90% confidence interval on log transformed Cmax, AUC0-t and AUC0-inffor pantoprazole fall within the acceptance criteria of 80% to 125%. No adverse events were observed.Conclusions:Pantoprazole powder for oral suspension 40 mg (sodium bicarbonate as buffer) was well tolerated and bioequivalent with pantoprazole enteric coated tablets IP 40 mg in terms of rate and extent of absorption under fasting conditions. At same time, the shift in AUC to the left with reduction in Tmaxwith the new formulation is suggestive of faster rate of absorption.

Commercial and Process Development of Pharmaceutical New Formulation and Optimization Technologies / 中国药学杂志

In order to get fast approval and market access, innovator pharmaceutical companies usually adopt the most mature and relatively simple formulations for their first generation new drug products. This leaves the opportunities for these products to improve their clinical performance, safety profiles and/or patient adherenceby switching to more sophisticated new formulations, which usually happen around the time when the patents for the new drugs expire. This approach may also work for older drugs. On the other hand, the task of new formulation and process development are more challenging forhigh-technology drug products based on, for examples, various controlled release formulations. In this article, the authors give a discussion regarding the thinking behind initiating the endeavor of new-formulation based development project. Based on the principles of Quality-by-Design, the authors also give a review regarding the trend of using experimental design, statistical and chemometric data analysis and multivariate modeling in formulation and process development. By analyzing examples in the literature, the authors try to demonstrate the advantages of designed studies vs. the traditional univariate methods.

Possibilities of Developing New Formulations for Better Skin Protection from a Traditional Medicinal Plant Having Potent Practical Usage.

Aims: Natural products obtained from different types of plants have made an important impact since ancient times throughout Asia. Since wood of Hesperethusa crenulata (Roxb.) Roem has been used traditionally by women in Southeast Asia for protection against sunlight and other harmful environmental factors, present study was aimed to determine antioxidant and antimicrobial properties of water extract of H. crenulata wood. Methodology: Wood was powdered, soaked in water, macerated, extracted fluid was lyophilized and tested for antioxidant and antimicrobial properties following standard techniques. The IC50 values were calculated from regression equations prepared from concentrations of extract and inhibition percent of free radical formation. The extract was screened for antimicrobial action following international guidelines against 44 organisms. Results: In DPPH assay system IC50 value was 344.74 μg/ml, the same for superoxide scavenging assay was 326.13μg/ml, while in hydroxyl radical scavenging system it was 999.85 μg/ml. Among 32 strains of staphylococci 10 strains were inhibited at 25 -50 μg /ml level of the extract, 6 strains at 100 μg /ml, 4 at 200 μg /ml and the remaining 12 strains were resistant. Strains of Bacillus spp and Vibrio vulnificus were rather sensitive to the extract, while E. coli and Pseudomonas aeruginosa were resistant. Thus the extract was inhibitory for bacteria known to invade human skin. Conclusions: The distinctly beneficial properties of the wood of H. crenulata indicate its usefulness as a highly active agent for the protection of skin against invasion by microorganisms and free radicals including those that may come from the sunlight.