Narendra Kumar Pandey

Nanosuspension: Principles, Perspectives and Practices

In the last three decades, nano-sizing of hydrophobic drugs has emerged as one of the most commonly used strategies to overcome their solubility and bioavailability related issues. Nanosuspensions offer versatile features and unique advantages over other approaches that have been utilized for this purpose. The unique inherent properties of nanosuspensions have been explored for a wide variety of applications. Commercial production of stable nanosuspensions has been made possible by the use of techniques such as media milling and high pressure homogenization. This article reviews various techniques being employed for production, characterization, merits and limitations of nanosuspensions and mechanisms that play a role in the physicochemical stability of nanosuspensions. The common strategies applied so far to overcome their stability and commercialization related aspects are also highlighted.

Formulation and characterization of ternary complex of poorly soluble duloxetine hydrochloride

Duloxetine hydrochloride (DXH) suffers from poor solubility and thereby poor absorption, which ultimately leads to poor bioavailability. In present study, an attempt has been made to formulate and characterize duloxetine hydrochloride (DXH) complex, using β-cyclodextrin (β-CD) and different hydrophilic polymers in order to enhance its solubility and dissolution rate. Phase solubility study was used to investigate the interaction of the drug in binary systems (DXH-β-CD) as well as ternary systems (DXH-β-CD-hydrophilic polymer). It was observed that solubilization of DXH by β-CD was further enhanced by using HPMC K4M at 0.1% w/v concentration. Several methods were used to prepare ternary complex of DXH-β-CD-HPMC K4M. Ternary complex prepared by co-evaporation method containing DXH-β-CD-HPMC K4M in the ratio of 1:1.10:0.01 has shown the fastest dissolution rate (53.65 ± 2.83% in 5 min) as compared to pure DXH (3.03 ± 1.88% in 5 min) as well as other methods used to prepare these complexes. The prepared ternary complex system was characterized by the help of X-ray powder diffraction studies, differential scanning calorimetry and scanning electron microscopy. It was observed that enhancement in solubility as well as dissolution rate of DXH was due to formation of ternary complex system.

Solidification of liquid Modified Apple Polysaccharide by its adsorption on solid porous carriers through spray drying and evaluation of its potential as binding agent for tablets

In the present study application of Modified Apple Polysaccharide (MAP) as tablet binder was evaluated. Liquid MAP was extracted from apple and solidified by adsorbing it on porous surface of Aerosil-200 and trehalose and this dispersion was dried using spray dryer. The concentration of excipients as well as spray drying conditions was optimised by using Box Behnken Design to achieve desirable powder characteristics. The optimised batch of solid MAP was characterized by DSC, PXRD, SEM, and FT-IR studies that confirmed complete adsorption of liquid MAP on the surface of Aerosil-200 and trehalose. This solid MAP was investigated for its binding efficacy for tablet formulation and its binding potential was compared with acacia and polyvinyl pyrrolidone K-30. Mesalamine (model drug) granules containing different concentration of binders were prepared by wet granulation. The granules were evaluated for micromeritic properties and results were found within the pharmacopoeial limits. The prepared tablets were subjected for post compression studies such as hardness, friability, disintegration, dissolution, physical stability, content uniformity and percentage elastic recovery and their results were found good. At 2.5% w/w concentration in tablet, the solid MAP has shown shorter disintegration time and faster dissolution profile as compared to other concentrations used including good physico-mechanical properties.

Impact of various solid carriers and spray drying on pre/post compression properties of solid SNEDDS loaded with glimepiride: in vitro-ex vivo evaluation and cytotoxicity assessment

Abstract Development of self-nanoemulsifying drug delivery systems (SNEDDS) of glimepiride is reported with the aim to achieve its oral delivery. Lauroglycol FCC, Tween-80, and ethanol were used as oil, surfactant, and co-surfactant, respectively as independent variables. The optimized composition of SNEDDS formulation (F1) was 10% v/v Lauroglycol FCC, 45% v/v Tween 80, 45% v/v ethanol, and 0.005% w/v glimepiride. Further, the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, dissolution, and diffusion. Both, liquid and solid-SNEDDS have shown release of more than 90% within 10 min. Results of permeation studies performed on Caco-2 cell showed that optimized SNEDDS exhibited 1.54 times higher drug permeation amount and 0.57 times lower drug excretion amount than that of market tablets at 4 hours (p < .01). Further, the cytotoxicity study performed on Caco-2 cell revealed that the cell viability was lower in SNEDDS (92.22% ± 4.18%) compared with the market tablets (95.54% ± 3.22%; p > .05, i.e. 0.74). The formulation was found stable with temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline glimepiride was observed in amorphous state in solid SNEDDS when characterized through DSC, PXRD, and FT-IR studies. The study revealed successful formulation of SNEDDS for glimepiride.

In-vitro and In-vivo Pharmacokinetic Evaluation of Guar Gum-Eudragit® S100 Based Colon-targeted Spheroids of Sulfasalazine Co-administered with Probiotics

BACKGROUND Polysaccharide based delivery systems have been successfully used to target drugs to colon. In some recent reports, the superiority of concomitant administration of probiotics with such systems has been established. However, the pharmacokinetics of such symbiotic therapy remain unexplored hitherto. METHODS This study deciphers the pharmacokinetic parameters of guar gum based colon targeted spheroids of sulfasalazine with co-administration of probiotics in experimental rats. Thirty rats were divided into five groups using Latin square design. These were subjected to treatment with delayed release formulation, uncoated spheroids, coated spheroid and coated spheroids along with probiotics. RESULTS In case of delayed release formulation, negligible presence of sulfasalazine in plasma was observed in first 2h, followed by significant increase in sulfasalazine concentration after 3h. Higher plasma concentrations of sulfasalazine were detected for uncoated spheroids with and without probiotics. Negligible release of drug upto 5h and delayed Tmax in case of guar-gum coated sulfasalazine spheroids with or without probiotics clearly indicated successful formulation of colon targeted spheroids. Further, for coated spheroids (both with and without probiotics), the value of Tmax is found to be significantly higher than those with the other treatments. CONCLUSION Colon targeted spheroids were therefore, found to reduce absorption of drug which, in turn, is expected to reduce the side effects as only local action in colon is required for treatment of colitis. This is the first report on pharmacokinetic study of a colon targeted delivery system co-administered with probiotics.