Modified apple polysaccharide capped gold nanoparticles for oral delivery of insulin.

The study entailed formulation of gold nanoparticles (AuNPs) upon reduction of chloroauric acid by modified apple polysaccharide (MAP). AuNPs were conjugated with insulin (INS) for its oral delivery to treat type 1 diabetes mellitus (DM). The size of MAP conjugated AuNPs loaded with INS was 124 ± 8.55 nm with zeta potential -10.5 ± 0.54 mV. The animal study carried out in streptozotocin induced rat model revealed that AuNPs conjugated insulin (AuNPs-INS) in high dose caused 3.36 folds decrease in blood glucose level in 240 min, whereas, orally administered INS failed to decrease the blood glucose level. The 28-day study also revealed better improvement in body weight, lipid profile, urea, creatinine and liver parameters in AuNPs-INS (high dose) for which the observed value was close with respect to intraperitoneally administrated insulin followed by medium dose of AuNPs-INS, low dose of AuNPS-INS, AuNPs alone and modified apple polysaccharide.

Quality by Design-Based Crystallization of Curcumin Using Liquid Antisolvent Precipitation: Micromeritic, Biopharmaceutical, and Stability Aspects.

The aim of present study was to introduce the role of quality by design to produce curcumin crystals with enhanced dissolution rate and bioavailability. The liquid antisolvent method was used to produce crystals. The crystal growth was controlled using the Box-Behnken design. The variables used in the crystallization process included the ratio of pyrocatechol to polyethylene glycol (PEG) 1500, solvent addition rate, stirring time, and stirring speed. Combination of these variables was found to yield curcumin crystals of 2.45 ± 0.56 µm size and 0.321 polydispersity index that exhibited enhanced solubility, dissolution rate, product yield, and compressibility. The optimized curcumin crystals were characterized by Fourier-transform infrared spectrophotometer (FT-IR), nuclear magnetic resonance, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. The dissolution rate and oral bioavailability of optimized curcumin crystals were found to be 2.66- and 7.08-folds higher than its unprocessed form. The optimized crystals were found stable for 6 months under accelerated temperature of 40°C and 75% relative humidity as there was no significant difference observed in the crystal size and dissolution profile.

A three-pronged formulation approach to improve oral bioavailability and therapeutic efficacy of two lipophilic drugs with gastric lability.

The aim of present study was to co-administer curcumin (CRM) liquisolid pellets and coated duloxetine hydrochloride (DXH) pellets in rats to treat neuropathic pain (NP) associated with chronic constriction injury (CCI). To formulate liquisolid pellets of CRM, it was first dissolved in Tween-80 and then adsorbed on the porous surface of MCC PH102 and Syloid XDP that were used as carrier and coating materials, respectively. Central composite design was used to optimize the liquisolid formulation. The results of powder X-ray diffraction studies, differential scanning calorimetry, and scanning electron microscopy showed complete solubility of drug in Tween-80 followed by its complete adsorption on the porous surface of Syloid XDP and MCC PH102. Both DXH and liquisolid CRM powders were converted into pellets using extrusion-spheronization. DXH pellets were further coated with Eudragit S100 to bypass the gastric pH. About 32.31-fold increase in dissolution rate of CRM present in liquisolid formulation was observed as compared to its unprocessed form. Similarly, the dissolution profile in 0.1 N HCl for Eudragit S100-coated DXH showed complete protection of drug for 2 h and complete release after its introduction in buffer medium (0.2 M phosphate buffer pH 6.8). he pharmacokinetic studies carried out on rats revealed 7.3-fold increase in bioavailability of CRM present in liquisolid pellets and 4.1-fold increase in bioavailability of DXH present in coated pellets was observed as compared to their unprocessed pellets. This increase in bioavailability of drugs caused significant amelioration of CCI-induced pain in rats as compared to their unprocessed forms. The histological sections showed better improvement in regeneration of nerve fibers in rats.

Efficacy of co-administration of modified apple polysaccharide and probiotics in guar gum-Eudragit S100 based mesalamine mini tablets: A novel approach in treating ulcerative colitis.

Modified Apple Polysaccharide (MAP) has been reported to cure colorectal diseases by up-regulating apoptosis and down regulating metastasis. In the present study, mesalamine (MES) and MAP mini tablets have been prepared and co-administered with probiotics to provide site specific release of drug. Probiotics along with MAP, which acts as a prebiotic would replenish the colonic microflora that have been compromised due to colorectal pathology. MES mini tablets were prepared keeping guar gum in the core and coating them with Eudragit S100 and guar gum. The optimized batch was explored for its curative potential on acetic acid induced ulcerative colitis (UC) in rat model with and without administration of probiotic and MAP. The results revealed that the rats treated with the combination of MAP and MES mini tablets along with probiotics show maximum curative potential. It was also observed that MAP mini tablets show better curative potential as compared to probiotics. The results of disease activity index, macroscopic scoring, antioxidant studies, tumour alpha and histopathological examination suggested that the rats treated with combination of MES-MAP mini tablets and probiotics have maximum therapeutic effect followed by MES mini tablets alone, MAP mini tablets alone and probiotics.

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.

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.