Design of a novel type IV lipid-based delivery system for improved delivery of drugs with low partition coefficient.

CONTEXT: The physicochemical properties of drugs such as partition coefficient play a major role in the development of lipid-based drug delivery systems. The major obstacle lies in encapsulation of a drug with low partition coefficient into these systems. OBJECTIVE: The objective of this study was to design and optimize a novel lipid-based delivery system with higher loading, improved pharmacokinetics consequently enhancing the oral bioavailability of drugs with low partition coefficient like valsartan. MATERIALS AND METHODS: The optimized formulation consists of Capryol 90, Cremophor RH 40, and Transcutol HP. Pseudo ternary phase diagrams were used to optimize the components and their concentrations in the formulation. Dissolution studies of the selected formulations were compared with plain drug and marketed product at three pH conditions (pH 1.2, 4.5 and 6.8). Pharmacokinetic parameters of optimized formulations were determined in Wistar rats and compared with that of plain drug. RESULTS AND DISCUSSION: The optimized formulation with a mean particle size of 50 nm showed significant improvement (p < 0.05) in dissolution rate with pH independence compared to plain drug and marketed product. The in vivo studies in Wistar rats revealed about 2.30- and 1.68-fold increase in the oral bioavailability and Cmax of valsartan from lipid-based formulation compared to plain drug. CONCLUSION: The engineered formulation strategy by type IV lipid-based formulations can be successfully exploited to improve the dissolution rate and oral deliverability of drugs like valsartan.

Large-scale STI services in Avahan improve utilization and treatment seeking behaviour amongst high-risk groups in India: an analysis of clinical records from six states.

BACKGROUND: Avahan, the India AIDS Initiative, implemented a large HIV prevention programme across six high HIV prevalence states amongst high risk groups consisting of female sex workers, high risk men who have sex with men, transgenders and injecting drug users in India. Utilization of the clinical services, health seeking behaviour and trends in syndromic diagnosis of sexually transmitted infections amongst these populations were measured using the individual tracking data. METHODS: The Avahan clinical monitoring system included individual tracking data pertaining to clinical services amongst high risk groups. All clinic visits were recorded in the routine clinical monitoring system using unique identification numbers at the NGO-level. Visits by individual clinic attendees were tracked from January 2005 to December 2009. An analysis examining the limited variables over time, stratified by risk group, was performed. RESULTS: A total of 431,434 individuals including 331,533 female sex workers, 10,280 injecting drug users, 82,293 men who have sex with men, and 7,328 transgenders visited the clinics with a total of 2,700,192 visits. Individuals made an average of 6.2 visits to the clinics during the study period. The number of visits per person increased annually from 1.2 in 2005 to 8.3 in 2009. The proportion of attendees visiting clinics more than four times a year increased from 4% in 2005 to 26% in 2009 (p<0.001). The proportion of STI syndromes diagnosed amongst female sex workers decreased from 39% in 2005 to 11% in 2009 (p<0.001) while the proportion of STI syndromes diagnosed amongst high risk men who have sex with men decreased from 12% to 3 % (p<0.001). The proportion of attendees seeking regular STI check-ups increased from 12% to 48% (p<0.001). The proportion of high risk groups accessing clinics within two days of onset of STI-related symptoms and acceptability of speculum and proctoscope examination increased significantly during the programme implementation period. CONCLUSIONS: The programme demonstrated that acceptable and accessible services with marginalised and often difficult-to-reach populations can be brought to a very large scale using standardized approaches. Utilization of these services can dramatically improve health seeking behaviour and reduce STI prevalence.