Oral bioavailability

Nanocochleates are unique novel drug delivery system in which, the desire drug molecule gets encapsulated into the multilayer of lipid crystal matrix. The nanocochleates structure provides protection to encochleated molecules from the degradation. It composed of negatively charged lipid generally phosphatidylserine and calcium. The nanocochleate structure has potential to carry the molecules which are hydrophobic, positively charged, negatively charged and that possess poor oral bioavailability. Nanocochleates is having more advantages than that of other dosage forms and system and hence it represents a new technology for oral and systemic delivery of drugs.

The aceclofenac sodium loaded calcium alginate (CA) based microbeads prepared by ionotropic external gelation technique with calcium chloride as cross-linking agent. Calcium alginate microbeads represent a useful tool for oral sustained/ controlled drug delivery but show several problems, mainly related to the stability, and rapid drug release at higher pH that, in most cases, is too fast due to increase porosity. To overcome such inconveniences, which was to develop CA microbeads coated with xyloglucan (XG) as drug release modifier to improve stability and prolong the drug release. The mean particle sizes of drug-loaded microbeads were found to be in the range 476.45±12 to 765.10 ± 0.22. The drug entrapment efficiency was obtained in the range of 62.24±0.66 to 102.75 ± 0.87.The shape and surface characteristics were determined by scanning electron microscopy (SEM). No significant drug-polymer interactions, physical changes and crystallinity of the drug in the formulations were determined by FT-IR spectroscopy, differential scanning calorimetry (DSC) and X-ray powder diffraction [XPRD]. In-vitro drug release profiles of microbeads were pH dependent and were analyzed by different kinetic models. The mechanism of drug release from microbeads depends on swelling and erosion process resulting CA microbeads was diffusion controlled followed by First order kinetics and whereas CA microbeads coated with XG approaching to near Zero- order kinetics.

The present study reports the role of the nanoparticulate drug delivery systems of rifampicin-lopinavir combinations on enhanced bioavailability of the drugs following oral administration. Entrapping both drugs in the ratio 1:1 is an additional objective. Poly (ethylene sebacate), a novel hydrolytically stable, nonionic, biocompatible and biodegradable, non-mutagenic and non-genotoxic polymer was selected for the study. PLGA and PLA were selected for comparative evaluation. Nanoparticles with adequate drug loading and particle size 350-450nm were developed and freeze dried using a combination of trehalose and lutrol-f-68 as cryoprotectant and characterized for zeta potential, hydrophobicity, SEM, DSC, pXRD etc. Nanoparticles found to be stable as per ICH guidelines. Pharmacokinetic evaluation of RIF-LOPI PES and PLGA nanoparticles revealed comparable plasma drug concentration, delayed Tmax and enhanced oral bioavailability, PLA nanoparticle revealed significantly higher bioavailability. T1/2 values were significantly higher with the nanoparticles for both RIF and LOPI. Following oral administration revealed high concentration of drugs in the RES organs lungs, liver and spleen compared to plain drugs was observed. The high bioavailability of both RIF and LOPI confirms the ability of nanoparticles both to enhance drug absorption and also provide protection in vivo. This protective effect of the nanoparticles enabled high bioavailability of LOPI despite being in combination with RIF an inducer of cytochrome P450.

The objective of the present study was to formulate a solid self micro emulsifying of drug delivery system (SMEDDS) for oral administration to improve the solubility and bioavailability of Lamotrigine. Solubility was determined in various oils, surfactants and cosurfactants. Ternary phase diagrams were constructed to evaluate the micro emulsification existence area. The optimized formula is obtained by factorial design employed as statistical tool.  The optimal formulation consists of 20% Capmul MCM C8, 55% Labrasol , 25% Tween 80 was adsorbed on carriers Aerosil200, Microcrystalline cellulose (MCC) .The solid SMEDDS are characterized by globule size analysis, and drug release studies of formulations are compared with plain drug. The pharmacokinetic study in rats for the optimized formulation was performed and compared to plain drug powder. SMEDDS have significantly increased the Cmax and area under the curve (AUC) of Lamotrigine compared to powder (P < 0.001). Thus, this self-micro emulsifying drug delivery system should been effective oral dosage form for improving oral bioavailability of Lamotrigine. Key Words: Solid self-microemulsifying drug delivery system, Globule size, Dissolution, Oral bioavailability