Trans-resveratrol (t-RVT) is a potent antioxidant. By virtue of extensive pre-systemic metabolism and existence of enterohepatic recirculation, t-RVT bioavailability is almost zero. The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides (LCTs) of t-RVT in an attempt to circumvent such obstacles. Equilibrium solubility studies indicated the choice of Lauroglycol FCC as lipid, and of Labrasol and Transcutol P as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X 1 ) and surfactant (X 2 ) as the critical factor variables. The SNEDDS were optimized using 3 2 central composite design (CCD) and the optimized formulation (OPT) located using overlay plot. The nanometer size range and high negative values of zeta potential depicted non-coalescent nature of the SNEDDS. Optimized formulation indicated marked improvement in drug release profile vis-à-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT. Augmentation in the values of K a (3.29-fold) and AUC (4.31-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT compared with pure drug. In situ perfusion (SPIP) studies in Wistar rats construed remarkable enhancement in the absorptivity and permeability parameters of SNEDDS vis-à-vis the pure drug. Successful establishment of level A of in vitro/in vivo correlation substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. The present study, therefore, reports the successful development of SNEDDS with distinctly enhanced bioavailability of t-RVT. KeywordsBioavailability, central composite design, in situ single pass intestinal perfusion, pharmacokinetic study, self-nanoemulsifying drug-delivery system History

The studies, therefore, could provide another useful tool for successful development of t-RVT NPs and an in vivo approach to designate nanoparticulate system of t-RVT with distinctly improved bioavailability and to overcome enterohepatic recirculation.

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Pioglitazone, a class II Biopharmaceutical Classification System drug having poor water solubility and slow dissolution rate may have a negative impact on its subtherapeutic plasma drug levels leading to therapeutic failure. In order to improve its water solubility and thus dissolution, cyclodextrin complexation technique was followed. The phase solubility studies were carried using three different types of cyclodextrins viz., β, methyl-β and γ-cyclodextrins. The Gibbs free energy was calculated in order to determine ease of the complexation. Binary systems of pioglitazone with cyclodextrins were prepared by kneading method and spray drying method. The phase solubility profiles with all the three cyclodextrins were classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complexes. The complexation capability of cyclodextrins with pioglitazone increased in the order of methyl-β > β > γ-cyclodextrin. The Gibbs free energy was found to be in the order γ > methyl-β > β cyclodextrin. Characterization of inclusion complexes was done by solubility studies, in vitro dissolution studies, Fourier transformation-infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry studies. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Greater solubility was observed with spray-dried methyl-β cyclodextrin complexes (2.29 ± 0.001 mg/ml) in comparison to the kneaded methyl-β cyclodextrin complexes (1.584 ± 0.053 mg/ml) and pure drug (0.0714 ± 0.0018 mg/ml).

The results, therefore, insight into the role of solubility enhancement and trounce enterohepatic recirculation for improving the oral bioavailability of t-RVT.

Human Immunodeficiency Virus (HIV) is a retrovirus that causes irreversible destruction of the immune system, leading to the occurrence of opportunistic infections and malignancies. During the last decade, even though attempts were being made to eradicate HIV, it was found that eradication of HIV is highly unlikely, and effective antiretroviral therapy is required on a long-term basis to maintain viral suppression and reduce disease progression. During this decade, effective therapies aimed at continued suppression of HIV replication and targeted at resting HIV reservoirs such as brain, lymphatic systems will be critical to prolong survival and renewing hopes for a cure. Currently available antiHIV drugs can be classified into three categories: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. Most of these drugs bear some significant drawbacks such as relatively short half-life, low bioavailability, poor permeability and undesirable side effects. Efforts have been made to design drug delivery systems for antiHIV agents to: a) reduce the dosing frequency, b) increase the bioavailability and decrease the degradation/metabolism in the gastrointestinal tract, c) improve the CNS penetration and inhibit the CNS efflux, and d) deliver them to the target cells selectively with minimal side effects. This article is an attempt to compile all major research work towards drug delivery for AIDS therapy and channel future attempts in the area of more effective controlled delivery of antiHIV agents.

Atazanavir (ATV) is a HIV protease inhibitor. Due to its intense lipophilicity, the oral delivery of ATV encounters several problems such as poor aqueous solubility, pH-dependent dissolution, rapid first-pass metabolism in liver by CYP3A5, which result in low bioavailability. To overcome afore mentioned limitations, ATV-loaded Eudragit RL100 nanoparticles (ATV NPs) were prepared to enhance oral bioavailability. ATV NPs were prepared by nanoprecipitation method. The ATV NPs were systematically optimized (OPT) using 3 2 central composite design (CCD) and the OPT formulation located using overlay plot. The pharmacokinetic study of OPT formulation was investigated in male Wistar rats, and in-vitro/in-vivo correlation level was established. Intestinal permeability of OPT formulation was determined using in situ single pass perfusion (SPIP) technique. Transmission electron microscopy studies on OPT formulation demonstrated uniform shape and size of particles. Augmentation in the values of K a (2.35-fold) and AUC 0-24 (2.91-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT formulation compared to pure drug. Successful establishment of in vitro/in vivo correlation (IVIVC) Level A substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. In situ SPIP studies ascribed the significant enhancement in absorptivity and permeability parameters of OPT formulation transport through the Peyer's patches. The studies, therefore, indicate the successful formulation development of NPs with distinctly improved bioavailability potential and can be used as drug carrier for sustained or prolonged drug release. KeywordsBioavailability, central composite design, nanoparticles, pharmacokinetic study, in situ single pass perfusion studies, in vitro/in vivo correlation History

Metformin hydrochloride (MH), a biguanide antidiabetic, is the drug of choice in obese patients. It is well absorbed from the upper part of gastrointestinal tract and has oral bioavailability of 50% to 60%. The objective of this study was to formulate MH into floating microspheres in order to increase its residence time at the site of absorption and thus improve its bioavailability; and to extend the duration of action along with possibilities of dose reduction. Microspheres were prepared by emulsion solvent evaporation method and evaluated for particle size, entrapment efficiency, buoyancy, and in vitro release; and further characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. The pharmacokinetic and pharmacodynamic evaluation of selected formulation was carried out in male Wistar diabetic rats. The data was statistically analyzed by unpaired t-test. A 3.5-fold increase in relative bioavailability was observed. The prolongation of half-life (t(1/2)) from 4.5 ± 2.41 h to 14.12 ± 4.81 h indicated extended duration of action. Oral glucose tolerance test (OGTT) was analyzed by one-way analysis of variance followed by Dunnet multiple comparison test, a significant decrease (p < 0.05) in the blood glucose levels was observed when formulations were compared with control rats. Hence, MH floating microspheres were tested at 50 mg/kg and 100 mg/kg body weight, OGTT data showed nonsignificant difference (p >0.05). In conclusion, an effective oral antidiabetics treatment can be achieved by formulating MH into floating microspheres which results in increase in bioavailability along with extended duration of action resulting in possible reduction in dose.