Chitosan-telmisartan polymeric cocrystals for improving oral absorption: In vitro and in vivo evaluation.

This study describes the development of polymeric cocrystals of chitosan-telmisartan (TEL) to improve the oral bioavailability of TEL, which has poor oral solubility and bioavailability. The polymeric cocrystal was prepared using chitosan a biopolymer with the aid of sodium citrate as a salting-out agent. The cocrystals were characterized by FT-IR spectroscopy, scanning electron microscopy, differential scanning calorimeteri (DSC), thermogravimetric analysis (TGA), and powder X-ray diffraction (PXRD). The improved solubility of TEL was observed with cocrystals as compared to that of pure drug in solubility studies with phosphate buffer (pH 7.4). The in vivo pharmacokinetics properties of cocrystal were studied by an animal model using rats after a single dose oral administration. The results showed an increased plasma drug concentration (Cmax) of 1.47, µg/ml for cocrystals when compared to pure TEL with 0.96 µg/ml with one-fold increased bioavailability (F%) that is, the cocrystals increases the solubility of the drug and the paracellular drug absorption by tight junction modulation. Further the elimination constant Kel resulted with higher value of about 0.0085 h-1 when compared to pure drug with0.0048 h-1 along with improved AUC (14.62 µg/ml).

Chitosan cocrystals embedded alginate beads for enhancing the solubility and bioavailability of aceclofenac.

Enhanced oral bioavailability of aceclofenac has been achieved using chitosan cocrystals of aceclofenac and its entrapment into alginate matrix a super saturated drug delivery system (SDDS). Prepared SDDS were evaluated by various physiochemical and pharmacological methods. The result revealed that the primary cocrystals enhanced the solubility of the drug and the thick gelled polymer matrix that formed from swelling of calcium alginate beads makes it to release the drug in continuous and sustained manner by supersaturated drug diffusion. The Cmax, Tmax and relative bioavailability for aceclofenac cocrystal and aceclofenac SDDS were 2.06±0.42 µg/ml, 1 h, 159.72±10.84 and 2.01 µg/ml, 1 h, 352.76±12.91, respectively. Anti-inflammatory activity of aceclofenac was significantly improved with the SDDS. With respect to the results, it revealed that the SDDS described herein might be a promising tool for the oral sustained release of aceclofenac and likely for that of various other poorly soluble drugs.

Development of duloxetine hydrochloride loaded mesoporous silica nanoparticles: characterizations and in vitro evaluation.

This study investigated the potential use of mesoporous silica nanoparticles (MSNs) as a carrier for duloxetine hydrochloride (DX), which is prone to acid degradation. Sol-gel and solvothermal methods were used to synthesize the MSNs, which, after calcination and drug loading, were then characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) technique, thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and diffuse reflectance ultraviolet-visible (DRS-UV-Vis) spectroscopy. Releases of DX from the MSNs were good in pH 7.4 (90%) phosphate buffer but poor in acidic pH (40%). In a comparative release study between the MSNs in phosphate buffer, TW60-3DX showed sustained release for 140 h, which was higher than the other nanoparticles. The mechanism of DX release from the MSNs was studied using Peppas kinetics model. The "n" value of all three MSNs ranged from 0.45 to 1 with a correlation coefficient (r (2)) >0.9, which indicated that the release of the drug from the system follows the anomalous transport or non-Fickian diffusion. The results supported the efficacy of mesoporous silica nanoparticles synthesized here as a promising carrier for duloxetine hydrochloride with higher drug loading and greater pH-sensitive release.

Optimization of chitosan succinate and chitosan phthalate microspheres for oral delivery of insulin using response surface methodology.

In the present study, a Box-Behnken experimental design was employed to statistically optimize the formulation parameters of chitosan phthalate and chitosan succinate microspheres preparation. These microspheres can be useful for oral insulin delivery system. The effects of three parameters namely polymer concentration, stirring speed and cross linking agent were studied. The fitted mathematical model allowed us to plot response surfaces curves and to determine optimal preparation conditions. Results clearly indicated that the crosslinking agent was the main factor influencing the insulin loading and releasing. The in vitro results indicated that chitosan succinate microspheres need high amount of crosslinking agent to control initial burst release compared to chitosan phthalate microspheres. The reason may be attributed that chitosan succinate is more hydrophilic than chitosan phthalate. The relative pharmacological efficacy for chitosan phthalate and chitosan succinate microspheres (18.66 +/- 3.84%, 16.24 +/- 4%) was almost three-fold higher than the efficacy of the oral insulin administration (4.68 +/- 1.52%). These findings suggest that these microspheres are promising carrier for oral insulin delivery system.

Design and development of gliclazide mucoadhesive microcapsules: in vitro and in vivo evaluation.

In this study an attempt was made to prepare mucoadhesive microcapsules of gliclazide using various mucoadhesive polymers designed for oral controlled release. Gliclazide microcapsules were prepared using sodium alginate and mucoadhesive polymer such as sodium carboxymethyl cellulose (sodium CMC), carbopol 934P or hydroxy propylmethyl cellulose (HPMC) by orifice-ionic gelation method. The microcapsules were evaluated for surface morphology and particle shape by scanning electron microscope. Microcapsules were also evaluated for their microencapsulation efficiency, in vitro wash-off mucoadhesion test, in vitro drug release and in vivo study. The microcapsules were discrete, spherical and free flowing. The microencapsulation efficiency was in the range of 65-80% and microcapsules exhibited good mucoadhesive property in the in vitro wash off test. The percentage of microcapsules adhering to tissue at pH 7.4 after 6 h varied from 12-32%, whereas the percentage of microcapsules adhering to tissue at pH 1.2 after 6 h varied from 35-68%. The drug release was also found to be slow and extended for more than 16 h. In vivo testing of the mucoadhesive microcapsules in diabetic albino rats demonstrated significant antidiabetic effect of gliclazide. The hypoglycemic effect obtained by mucoadhesive microcapsules was for more than 16 h whereas gliclazide produced an antidiabetic effect for only 10 h suggesting that mucoadhesive microcapsules are a valuable system for the long term delivery of gliclazide.

Development and in-vivo evaluation of insulin-loaded chitosan phthalate microspheres for oral delivery.

Novel chitosan phthalate microspheres containing insulin were prepared by emulsion cross-linking technique. The feasibility of these microspheres as oral insulin delivery carriers was evaluated. The pH-responsive release behaviour of insulin from microspheres was analysed. The ability of chitosan phthalate-insulin microspheres to enhance intestinal absorption and improve the relative pharmacological availability of insulin was investigated by monitoring the plasma glucose and insulin level of streptozotocin-induced diabetic rats after oral administration of microspheres at insulin dose of 20 IU kg(-1). In simulated gastric fluid (pH 2.0), insulin release from the microspheres was very slow. However, as the pH of the medium was changed to simulated intestinal fluid (pH 7.4), a rapid release of insulin occurred. The relative pharmacological efficacy for chitosan phthalate microspheres (18.66 +/- 3.84%) was almost four-fold higher than the efficacy of the chitosan phthalate-insulin solution administration (4.08 +/- 1.52%). Chitosan phthalate microspheres sustained the plasma glucose at pre-diabetic level for at least 16 h. These findings suggest that the microsphere is a promising carrier as oral insulin delivery system.

Development and characterization of chitosan succinate microspheres for the improved oral bioavailability of insulin.

The present study describes the fabrication of insulin loaded chitosan succinate microspheres to improve the efficacy of orally administered insulin. Chitosan succinate polymer was synthesized and its microspheres were prepared by emulsion phase separation technique. The microspheres were characterized by FT-IR spectroscopy, scanning electron microscopy, particle size, X-ray diffraction, and swelling index. Insulin was loaded into the microspheres by passive absorption technique. The ability of microspheres to protect insulin from gastric enzymatic degradation was investigated. Stability of insulin in the microspheres was determined by gel electrophoresis and circular dichroism (CD). In vitro release studies were performed under simulated gastric and intestinal pH conditions (pH 2.0 and pH 7.4). The pharmacokinetic parameters were monitored after oral administration of insulin loaded chitosan succinate microspheres, chitosan succinate-insulin solution, as well as after subcutaneous injection of insulin to diabetic rats. The degree of succinate substitution in the synthesized polymer was 16%. The prepared microspheres were spherical with an average diameter of 49 +/- 2 microm. The insulin-loading capacity was 62%. Chitosan succinate microspheres were found to protect the degradation of insulin from gastric enzymes. The encapsulated insulin was quickly released in simulated intestinal fluid (SIF, pH 7.4), whereas a small fraction of insulin was released in simulated gastric fluid (pH 2.0). The relative pharmacological efficacy for chitosan succinate microspheres (16 +/- 4%) was almost fourfold higher than the efficacy of the chitosan succinate-insulin solution administration (4 +/- 1.5%). The results suggest that chitosan succinate microspheres could be used as a potential carrier for oral insulin delivery.

Transdermal therapeutic system of carvedilol: effect of hydrophilic and hydrophobic matrix on in vitro and in vivo characteristics.

The purpose of this research was to develop a matrix-type transdermal therapeutic system containing carvedilol with different ratios of hydrophilic and hydrophobic polymeric combinations by the solvent evaporation technique. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. In vitro permeation studies were performed by using Franz diffusion cells. The results followed Higuchi kinetics (r = 0.9953-0.9979), and the mechanism of release was diffusion mediated. Based on physicochemical and in vitro skin permeation studies, patches coded as F3 (ethyl cellulose:polyvinylpyrrolidone, 7.5:2.5) and F6 (Eudragit RL:Eudragit RS, 8:2) were chosen for further in vivo studies. The bioavailability studies in rats indicated that the carvedilol transdermal patches provided steady-state plasma concentrations with minimal fluctuations and improved bioavailability of 71% (for F3) and 62% (for F6) in comparison with oral administration. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied using methyl prednisolone acetate-induced hypertensive rats. It was observed that both the patches significantly controlled hypertension from the first hour (P < .05). The developed transdermal patches increase the efficacy of carvedilol for the therapy of hypertension.