Bioavailability enhancement of voriconazole using liposomal pastilles: Formulation and experimental design investigation.

Oral mucosa offers several advantages in the delivery of therapeutic molecules. It avoids presystemic metabolism, Nanoencapsulation techniques might be applied to conquer physical, chemical challenges and enhance drug penetration, formulation performance, prolonging drug residence time, and improving sensorial feeling. The present investigation is aimed to formulate liposomal pastilles with high bioavailability. Voriconazole Liposomes (VL) were produced by utilizing varied ratios of soya lecithin (SL) and cholesterol (CH) by solvent Injection method. RSM is utilized to identify the optimized formulation, as this design provides a thorough understanding of a process and also has great utilization in originating the robustness of the product. The main impact and interaction terms of the formulation variables were assessed quantitatively utilizing a mathematical-statistical approach indicating that both independent variables have significant ('P' value < 0.05) effects on particle size ('P' value: 0.0142), percentage entrapment efficiency ('P' value: 0.0120), percentage drug release through the dialysis membrane ('P' value: 0.0105), percentage drug release through porcine buccal mucosa ('P' value: 0.0171) and percentage zone of inhibition ('P' value: 0.0305). Optimal liposomal encapsulated in noticed in 15:10 lecithin: cholesterol concentration (VLP-6). Higher Lecithin and Cholesterol quantity in the liposome formulations resulted in lower drug entrapment efficiency and drug release when compared with middle levels of lecithin and cholesterol content formulation. The pastilles were prepared from the optimized liposomal formulation with a modified method reported in British Pharmaceutical Codex, 1907. These liposomal pastilles were subjected to evaluation of physicochemical parameters, In vitro drug release studies, stability studies, and In vivo bioavailability studies in comparison with pure voriconazole pastilles (PVP). The statistical data analysis results indicated that there was a significant difference in Tmax, Ka, t1/2 abs, t1/2 elim, AUC0-24, AUC0-∞, AUMC0-24 and AUMC0-∞, values among PVP and VLP-6. There was no significant difference in Cmax, Kel, MRT0-24 and MRT0-∞values among pure voriconazole pastilles and optimized liposomal formulation.

Effect of niacin on triglyceride-rich lipoprotein apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes.

AIM: To investigate the effects of extended-release (ER) niacin on apolipoprotein B-48 (apoB-48) kinetics in statin-treated patients with type 2 diabetes (T2DM). METHODS: A total of 12 men with T2DM were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed to the alternate therapy. Postprandial metabolic studies were performed at the end of each treatment period. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. ApoB-48 kinetics were determined using stable isotope tracer kinetics with fractional catabolic rates (FCRs) and secretion rates derived using a non-steady-state compartmental model. Area-under-the-curve (AUC) and incremental AUC (iAUC) for plasma triglyceride and apoB-48 were also calculated over the 10-h period after ingestion of the fat meal. RESULTS: In statin-treated patients with T2DM, apoB-48 concentration was lower with ER niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/l, p = 0.03) compared with statin alone. Postprandial triglyceride and apoB-48 AUC were also significantly lower on ER niacin treatment (-15 and -26%, respectively; p < 0.05), without any change to triglyceride and apoB-48 iAUC. ApoB-48 secretion rate in the basal state (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p = 0.04) and number of apoB-48-containing particles secreted in response to the fat load (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p = 0.02) were lower on ER niacin. ApoB-48 FCR was not altered with ER niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p = 0.79). CONCLUSIONS: ER niacin reduces apoB-48 concentration by lowering fasting and postprandial apoB-48 secretion rate. This effect may be beneficial for lowering atherogenic postprandial lipoproteins and may provide cardiovascular disease risk benefit in patients with T2DM.

Formulation and Evaluation of Rifampicin Liposomes for Buccal Drug Delivery.

BACKGROUND: Drug delivery through liposomes offers several advantages, but still challenging to the researchers for the use of liposomes as carriers in drug delivery due to their poor physical stability, unpredictable drug encapsulation and systemic availability of the loaded drug. OBJECTIVE: The present investigation was planned with an objective to prepare Rifampicin loaded liposomes by using response surface methodology of statistical 32 factorial design and further to formulate them into pastilles for deliver through buccal route thereby to enhance systemic absorption. METHODS: Rifampicin liposomes were prepared by using different ratios of soya lecithin and cholesterol by solvent Injection method. These liposomes were characterized by using optical microscopy, Scanning Electron Microscopy (SEM) and evaluated for particle size, entrapment efficiency (EE), in vitro and ex vivo drug release. RESULTS: Main effects and interaction terms of the formulation variables were evaluated quantitatively using a mathematical statistical model approach showing that both independent variables have significant (P value < 0.05) effects on particle size (P value: 0.0273), percentage entrapment efficiency (P value: 0.0096), percentage drug release through dialysis membrane (P value: 0.0047) and percentage drug release through porcine buccal membrane (P value: 0.0019). CONCLUSION: The statistical factorial design of liposomal formulations fulfilled all the requirements of the target set and exhibited suitable values for the selected test parameters. Pastilles were prepared for liposomes using glycerol gelatin base and were found to be soft, smooth with uniform drug content and drug release.