Utpal Kumar Sanki

Bio: Utpal Kumar Sanki is an academic researcher from VIT University. The author has contributed to research in topics: Bioequivalence & Elimination rate constant. The author has an hindex of 2, co-authored 4 publications receiving 8 citations.

Comparative pharmacokinetics study of two different clindamycin capsule formulations: a randomized, two-period, two-sequence, two-way crossover clinical trial in healthy volunteers.

Abstract: The comparative pharmacokinetic (PK) study of two brands of clindamycin hydrochloride (CAS 21462-39-5) was carried out on 32 healthy Indian subjects in an open label randomized, two way crossover, two period, two sequence, two treatment trial with a minimum washout period of 7 days. Plasma samples were collected at 10 min interval for the 1st hour, at 1 h interval for the next 6 h, at 2 h interval for next 12 h and finally at the 24th hour (pre-dose as baseline value) after drug administration. The concentrations of clindamycin in plasma were determined using high performance liquid chromatography (HPLC) technique with UV detector [lower limit of quantitation (LLOQ) 0.05 microg x mL(-1)). All PK parameters were calculated from data on clindamycin content in plasma using a non-compartmental model. Primary PK parameters were maximum plasma concentration (Cmax), area under the curve from zero to t(th) hour (AUCT) and area under the curve from zero to infinite (AUCI), whereas secondary PK parameters were elimination half-life (t half), elimination rate constant (K el) and time to reach maximum plasma concentration (Tmax). All primary PK parameters (log transformed) were subjected to ANOVA analysis and two one-sided Student's t-test (TOST) to construct the 90% confidence intervals. The result of ANOVA showed that all primary PK parameters at 90% confident intervals were within the limit of 80-125%. All the values such as 95.7-109.00% for Cmax, 99.5-117% for AUCT and 99.1% to 114% for AUCI showed pharmacokinetic equivalence and indicated that this comparative pharmacokinetic study was well designed to conclude that the test formulation and reference formulation were pharmacokinetically equivalent and hence bioequivalent with respect to rate and extent of absorption.

In Vitro-In Vivo Correlation Evaluation of Generic Alfuzosin Modified Release Tablets

Abstract: Alfuzosin, a selective alpha-1a antagonistis is the most recently approved AARAS, with limited cardiac toxicity and exclusively used for lower urinary tract syndromes (LUTS). In order to reduce pill burden and better patient compliance modified release (MR) formulations have been developed. Alfuzosin MR tablet was developed by the use of hot-melt granulation techniques using monoand diglycerides as rate controlling membranes to minimize health care cost and uses of costly excipients. The other purpose of the study was to evaluate in vitro-in vivo performance of the scale up batch in healthy human subjects for commercialization. The blend uniformity (mean ± RSD%), assay, cumulative percent dissolution at 24h, hardness, and friability of the biobatch were 100.2 ± 0.05%, 100.43 ± 0.023%, 93.98%, 4.5kg, 5min, and 0.08%, respectively. The in vivo pharmacokinetic parameters under fasting conditions between test and reference formulations (Uroxatral 10mg extended release tablets) were comparable. The 90% CI, geometric mean ratio (%) and power of Cmax, AUCT, and AUCI of the fasting study for the test and reference formulation were 99.03% to 122.78%, 109%, 0.998; 92.94% to 116.71%, 104%, 1; 98.17% to 124.01%, 110% 1, respectively. The scale up biobatch showed negligible difference in in vitro properties with respect to the pilot batch. The formulation developed with these agents was safe to use as there were no serious adverse events developed during the conduction of the clinical trial on the healthy subjects. Furthermore, the developed formulation was bioequivalent with respect to rate and extends of absorption to the reference formulation.

Reference-scaled average bioequivalence study of paroxetine under fed conditions: validation of sample size estimation by bootstrapping technique

Abstract: Objective: New technique was adopted and validated to estimate pivotal sample size from the pilot study data and to establish bioequivalence (BE) of highly variable drugs (HVD), paroxetine, a novel controlled release (CR) matrix tablets utilized ghatti Gum as a rate controlling membrane, in human subject under fed conditions by reference scale design. Methods: Bootstrapping technique was adopted to calculate the pivotal sample size from pilot study data for HVD paroxetine. The reliability and validation of the method were tested in a semi replicate three sequence (RRT, RTR, and TRR where T stand for test drug and R stand for reference drug) cross-over BE study in 24 healthy subjects under fed conditions. Results: The ratio of the pharmacokinetic (PK) metric obtained from the bootstrapping technique after log transformation was 1.04 for Cmax, 1.23 for AUCT, and 1.21 for AUCI with corresponding power of the study which was greater than 80% from pilot study data simulation. The ratio of the PK metric obtained from the reference scaling design in the present study was 1.00 for Cmax, 1.21 for AUCT, and 1.17 for AUCI. The upper limit of the Cmax, AUCT, and AUCI at 95% confidence limit was −0.143, −0.136, and −0.17, respectively. Conclusion: The test paroxetine CR formulation was bioequivalent with reference drug under fed conditions. The technique used for estimation of the sample size in the pivotal study was found reliable, and bootstrapping technique plays an important role in calculating sample size where intrasubject variability was immaterial.

Mixed scaling approach to establish bioequivalence of lansoprazole delayed release capsule in fasting sprinkle with apple sauce study in healthy subjects

Abstract: Objective: The aim of the present study was to establish bioequivalence of highly variable generic lansoprazole (LSP) delayed release (DR) capsule, exploring minimal number of healthy volunteers by mixed scaling approach as oppose to average bioequivalence approach. Methods: This was an open-labeled, three-treatment, three-periods, three-sequences, single-dose, partial replicate crossover trial conducted in 36 + 4 (stand by) healthy adult human subject in Indian origin. Results: Non-parametric Wilcoxon sign rank test at 95% confidence interval failed to conclude significance difference in T and t1/2 between the formulations. The intra subject standard deviation of the reference formulation was 0.340 for C , 0.249 for area under curve up to last measurable time point (AUCT) and 0.244 for area under curve up to infinity time (AUCI) parameters. The reference scaling as proposed by Haider et al., 2008, was applied for C max, max and constant scaling was applied for AUCT and AUCI metrics. No significance difference between two formulations were observed when data were analyzed by Analysis of Variance (p<0.05). Westlake 90% confidence limit, as well as two one-sided t-test as proposed by Schuriman and the Anderson-Hauck power analysis all fell under the predefine bioequivalence criteria for mixed scaling. Conclusion: The generic LSP DR capsules were found to bioequivalent with reference drug under fasting study with apple sauce with respect to rate and extent of absorption. The mixed scaling statistical analysis approach used to establish bioequivalence with a minimum number of subjects was found reliable and utilize 40 subjects as opposed to 110 subjects need to establish bioequivalence in traditional average bioequivalence approach. Keywords: Mixed scaling, Techniques, Non-parametric, Bioequivalence, Delayed release.

Square-wave voltammetric determination of clindamycin using a glassy carbon electrode modified with graphene oxide and gold nanoparticles within a crosslinked chitosan film

Abstract: An electrochemical method for the determination of clindamycin using a glassy carbon electrode modified with graphene oxide and gold nanoparticles within a film of crosslinked chitosan with epichlorohydrin (AuNPs-GO-CTS-ECH/GCE) is proposed. The electrochemical behavior of clindamycin was studied using cyclic voltammetry, and square-wave voltammetry (SWV). Under the optimized working conditions using 0.1 mol L−1 phosphate buffer (pH 7.0) solution as the supporting electrolyte, at a potential of +0.8 V vs. Ag/AgCl (3.0 mol L−1 KCl), using the SWV technique with the proposed AuNPs-GO-CTS-ECH/GCE electrode, the analytical curve showed a wide linear concentration range from 9.5 × 10−7 to 1.4 × 10−4 mol L−1, with a limit of detection of 2.9 × 10−7 mol L−1. The voltammetric method was successfully applied in the quantification of clindamycin in pharmaceutical formulations, as well as synthetic urine and river water samples, with results similar to those obtained by a comparative method (HPLC).

Interethnic Differences in Pharmacokinetics of Antibacterials

Abstract: Optimal antibacterial dosing is imperative for maximising clinical outcome. Many factors can contribute to changes in the pharmacokinetics of antibacterials to the extent where dose adjustment may be needed. In acute illness, substantial changes in important pharmacokinetic parameters such as volume of distribution and clearance can occur for certain antibacterials. The possibility of interethnic pharmacokinetic differences can further complicate attempts to design an appropriate dosing regimen. Factors of ethnicity, such as genetics, body size and fat distribution, contribute to differences in absorption, distribution, metabolism and elimination of drugs. Despite extensive previous work on the altered pharmacokinetics of antibacterials in some patient groups such as the critically ill, knowledge of interethnic pharmacokinetic differences for antibacterials is limited. This systematic review aims to describe any pharmacokinetic differences in antibacterials between different ethnic groups, and discuss their probable mechanisms as well as any clinical implications. We performed a structured literature review to identify and describe available data of the interethnic differences in the pharmacokinetics of antibacterials. We found 50 articles that met our inclusion criteria and only six of these compared antibacterial pharmacokinetics between different ethnicities within the same study. Overall, there was limited evidence available. We found that interethnic pharmacokinetic differences are negligible for carbapenems, most β-lactams, aminoglycosides, glycopeptides, most fluoroquinolones, linezolid and daptomycin, whereas significant difference is likely for ciprofloxacin, macrolides, clindamycin, tinidazole and some cephalosporins. In general, subjects of Asian ethnicity achieve drug exposures up to two to threefold greater than Caucasian counterparts for these antibacterials. This difference is caused by a comparatively lower volume of distribution and/or drug clearance. Interethnic pharmacokinetic differences of antibacterials are likely; however, the clinical relevance of these differences is unknown and warrants further research.

Cross-linked poly(vinyl alcohol) nanofibers as drug carrier of clindamycin

Abstract: Given the importance of nanofibers in the field of pharmaceutical sciences and drug delivery applications, this study aimed to use poly(vinyl alcohol) (PVA) nanofibers as drug carriers for clindamycin. First, PVA solution was electrospun without drug to obtain electrospinning optimum condition of reference carrier. Then, 8% PVA solution containing 2% clindamycin was electrospun under optimum conditions at 20 kV voltage, 10 cm for nozzle-to-collector distance and an injection rate of 1 mL/h. In order to control drug release and improve the surface wet ability, the prepared polymeric nanofibers were cross-linked by glutaraldehyde. The prepared mats of nanofibers were characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared and contact angle analysis. The in vitro drug release from nanofibers into the phosphate-buffered saline solution was measured by high-performance liquid chromatography at a wavelength of 210 nm. The in vitro drug release showed that cross-linked nanofibers had a lower drug release rate in a longer time.