The central nervous system (CNS) is an immunological privileged sanctuary site-providing reservoir for HIV-1 virus. Current anti-HIV drugs, although effective in reducing plasma viral levels, cannot eradicate the virus completely from the body. The low permeability of anti-HIV drugs across the blood-brain barrier (BBB) leads to insufficient delivery. Therefore, developing a novel approaches enhancing the CNS delivery of anti-HIV drugs are required for the treatment of neuro-AIDS. The aim of this study was to develop intranasal nanoemulsion (NE) for enhanced bioavailability and CNS targeting of saquinavir mesylate (SQVM). SQVM is a protease inhibitor which is a poorly soluble drug widely used as antiretroviral drug, with oral bioavailability is about 4%. The spontaneous emulsification method was used to prepare drug-loaded o/w nanoemulsion, which was characterized by droplet size, zeta potential, pH, drug content. Moreover, ex-vivo permeation studies were performed using sheep nasal mucosa. The optimized NE showed a significant increase in drug permeation rate compared to the plain drug suspension (PDS). Cilia toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVM-loaded NE. Results of in vivo biodistribution studies show higher drug concentration in brain after intranasal administration of NE than intravenous delivered PDS. The higher percentage of drug targeting efficiency (% DTE) and nose-to-brain drug direct transport percentage (% DTP) for optimized NE indicated effective CNS targeting of SQVM via intranasal route. Gamma scintigraphy imaging of the rat brain conclusively demonstrated transport of drug in the CNS at larger extent after intranasal administration as NE.

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Most of the new chemical entity suffers from low bioavailability due to their low aqueous solubility and dissolution. Many approaches have been used like micronization, solubilization, complexation with polymer, salt formation, use of prodrug, addition of surfactant, solid dispersions, etc. But all these methods suffer from limitations like size reduction by micronization, form surface charges which show poor flow property.1) Amorphous system exhibits significant solubility benefits, due to excess thermodynamic properties and lower energetic barrier than its crystalline form.2) The major reason for limited solubility benefit from amorphous system is their devitrification, on exposure to primary aqueous dissolution medium. This limited solubility can be overcome by further increases in solubility by preparing solid dispersions (SD) with polymer having high glass transition temperature (Tg) value like hydroxypropyl methylcellulose (HPMC), polyvinyl pyrrolidone (PVP).3) SD increases the solubility by slowing devitrification, and increased wettability due to hydrophilic nature.4) Solid dispersion is useful method to disperse drugs in the molecular state in a carrier matrix. 5,6) Various methods have been reported for preparation of solid dispersion like physical mixture, kneading method, spray drying, solvent wetting, and modified solvent evaporation method. 7) Most of these methods are amenable only to research laboratory set up, with the exception of spray drying, which can be scaledup industrially. 8) Solid dispersions by spray drying technique has been reported for wide variety of poorly aqueous soluble drug like glibenclamide, 9) curcumin, 10) albendazole, 11) tolbutamide, 12) loperamide. [4,4]non-1-en-4-one antagonizes angiotensin II by blocking AT 1 receptors is indicated for treatment of hypertension.14) It belongs to class II drug according to biopharmaceutical classification system (BCS) i.e. low solubility and high permeability. According to BCS drug substance is considered to be highly soluble when highest dose of drug dissolve in less than 250 ml of water. It is considered to be highly permeable when the extent of absorption in human is more than 90% of an administered dose. Although it has excellent oral bioavailability (60-80%), but theoretically IBS exhibits solubility limited bioavailability and it would be advantageous to increase the solubility of such molecule.15) Solubility of IBS was found to be increased after complexation with polymer like b-cyclodextrin. 16)In this study solid dispersions of IBS were prepared by spray drying technique using low viscosity grade of HPMC E5 LV having the high Tg value in order to enhance its solubility, dissolution rate and bioavailability. Spray drying technique has advantages like generation of amorphous system and formation of solid dispersions simultaneously. The physical properties of the prepared solid dispersions were characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffractometry (PXRD), Fourier ...

The aim of this study was to investigate the potential application of thermosensitive gels formed by a xyloglucan polysaccharide derived from tamarind seed for nasal drug delivery. Xyloglucan that had been partially degraded by β-galactosidase to eliminate 45% of galactose residues formed gels at concentrations of 2.5% w/w at gelation temperatures decreasing over the range 27-28°C. The in vitro release of ondansetron hydrochloride from the enzyme-degraded xyloglucan gels followed higuchi kinetics over a period of 5 h at 34°C by anomalous transport mechanism. The ex vivo permeation of ondansetron hydrochloride from the gels was sustained. Histological examination of nasal mucosa following a single administration of the gels showed no evidence of mucosal damage. Finally, the bioavailability study in rabbits revealed that the absolute bioavailability of ondansetron hydrochloride was significantly increased from 28.64% in the case of the oral drug solution to 52.79% in the case of the nasal in situ gel. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for nasal delivery of drugs.

The purpose of the present research work was to extract linseed mucilage, use it as a mucoadhesive agent and to develop mucoadhesive microspheres for buccal delivery with an intention to avoid hepatic first-pass metabolism, by enhancing residence time in the buccal cavity. Linseed mucilage was extracted and used to prepare microspheres with varying concentrations of mucilage from formulation F1-F4 (1-2.5%) by spray-drying technique. The microspheres were evaluated for the yield, particle size, incorporation efficiency, swelling property, in vitro mucoadhesion, in vitro drug release, histological study, and stability. Microspheres were characterized by differential scanning colorimetry, scanning electron microscopy, and X-ray diffraction study. Further, the bioavailability study using the New Zealand rabbits was carried out. Formulation F4 showed the maximum mucoadhesion 89.37 ± 1.35%, 92.10 ± 1.37% incorporation efficiency, highest swelling index 0.770 ± 1.23. F4 showed a marked increase in the bioavailability after buccal administration (51.86 ± 3.95) as compared to oral route (39.60 ± 6.16). Also it took less time to reach maximum plasma concentration of 21.38 ± 1.05 ng/ml as compared to oral solution where it required 180 min to reach maximum plasma concentration of 17.98 ± 1.14. It is concluded from the results that linseed mucilage can be used in the production of the mucoadhesive microspheres.