Effect of dodecylmaltoside (DDM) on uptake of BCS III compounds, tiludronate and cromolyn, in Caco-2 cells and rat intestine model.

The efficacy of n-lauryl-beta-D-maltopyranoside, (dodecylmaltoside, DDM) as a permeability-enhancer for tiludronate and cromolyn (BCS Class III, water-soluble compounds with oral bioavailability < 5%) was evaluated in Caco-2 cell monolayers and rat intestinal sacs. In Caco-2 cells samples were collected over a 5-h period and transepithelial resistance (TEER) was measured concurrently. In rat intestinal sacs, samples of the test compounds and marker (Lucifer Yellow) were collected over a 40 min period; accumulation in the serosal fluid and intestinal tissue was measured. At lower concentration DDM had no effect on cromolyn permeability and a marginal increase was observed at higher concentration. Tiludronate permeability in the presence of DDM showed greater enhancement as compared to cromolyn. At higher concentration DDM appeared to cause permanent damage to the cell monolayer (irreversible change in TEER). In the intestinal tissue, DDM caused increased tissue accumulation of test compounds. This indicated that transport was not restricted to the paracellular route and damage to the intestinal tissue could not be ruled out. Based on the results obtained in this study it can be concluded that at concentrations that are non-toxic DDM appears to have a limited use to improve the oral absorption of cromolyn and tiludronate.

Improved delivery of cromolyn from oral proliposomal beads.

Proliposomal bead formulations for improved oral delivery of cromolyn (BCS Class III compound) were formulated. Phospholipid (distearylphosphatidylcholine)-cholesterol-surfactant (Tween 80/sodium cholate) systems were spray-coated on beads containing cromolyn sodium and the dosage forms were characterized for vesicle formation and encapsulation efficiency. Delivery of cromolyn sodium from this novel dosage form was evaluated across the Caco-2 and everted rat intestinal sac model. Spontaneous formation of vesicles upon dilution of beads was observed. Enhancement in cromolyn transport was higher with phospholipids-surfactant proliposomal formulations compared to surfactant-free lipid formulations or pure surfactant solutions, most significant enhancement being with formulations with low surfactant concentration. No evidence of cellular damage to Caco-2 monolayers (e.g. significant decrease in the TEER) or change in transport and tissue accumulation of a marker molecule in the intestinal tissue model was observed. This indicated enhancement of transport via transcellular routes and not due to the modulation of the tight junctions or cell disruption. Results suggest that phospholipids-surfactant proliposomal beads offer a good potential for improved oral delivery of cromolyn.

Private practitioners' communications with patients around HIV testing in Pune, India.

Unlike any other disease so far, the 'exceptional' nature of HIV/AIDS has prompted debate about the necessity, but also the challenges, of regulating practitioner-patient communication around HIV testing. In India, the National AIDS Control Organization (NACO) has adopted the guidelines of the World Health Organization with regard to HIV testing and counselling, yet the extent to which these guidelines are fully understood or followed by the vast private medical sector is unknown. This paper examines the gaps between policy and practice in communications around HIV testing in the private sector and aims to inform a bottom-up approach to policy development that is grounded in actual processes of health care provision. Drawing on 27 in-depth interviews conducted with private medical practitioners managing HIV patients in the city of Pune, we looked specifically at practitioners' reported communications with patients prior to an HIV test, during and following disclosure of the test result. Among these practitioners, informed consent is rare and pre-test communication is prescriptive rather than shared. Confidentiality of the patient is often breached during disclosure, as family members are drawn into the process without consulting the patient. While non-adherence to guidelines is a matter of concern, practitioners' communication practices in this setting must be understood in the given social and legal context of the patient-practitioner relationship in India. Communication with their patients is strongly influenced by practitioners' perceptions of their own roles and relationships with patients, perceived characteristics of the patient population, limitations in knowledge and skills, moral values as well as perceptions of legal guidelines and patient rights. We suggest that policy guidelines around patient-practitioner communication need to take sufficient cognizance of existing practices, cultures and the realities of care provision in the private sector. Patients themselves need to be empowered in order to grasp the importance and implications of HIV testing and counselling.

Managing uncertainty around HIV/AIDS in an urban setting: private medical providers and their patients in Pune, India.

Changing epidemiological patterns and the advent of new rapid diagnostic technologies and therapies have created considerable uncertainty for providers working in HIV. In India, the demand for HIV care is increasingly being met by private practitioners (PPs), yet little is known about how they deal with the challenges of managing HIV patients. To explore HIV management practices in the private medical sector, a survey was conducted with 215PPs in Pune, India, followed by in-depth interviews focusing on the social context of practice among a sub-set of 27PPs. Drawing primarily on interview data, this paper illustrates a number of uncertainties that underlie the reported actions of providers in a competitive medical market. PPs perceive HIV as a 'new' and challenging disease for which they lack adequate knowledge and skills. Combined with the perceived high cost and complexity of antiretroviral treatment, preconceptions about HIV patients' social, financial and mental capacity lead to highly individualistic management practices. While these fall short of clinical 'best practice' guidelines, they reflect adaptive responses to the wider uncertainties surrounding HIV care in urban India. By highlighting contextual issues in PPs' management of HIV patients, the paper suggests the need to explicitly acknowledge the social, moral and economic bases of uncertainty beyond the clinical setting.

Urban private practitioners: potential partners in the care of patients with HIV/AIDS.

BACKGROUND: The private medical sector is an important source of healthcare in India. Increasingly, concerns have been raised about its role in the care of patients with HIV/AIDS. Evidence about private practitioners' existing management practices will help to create policies addressing this sector. METHODS: A central urban area of Pune city was selected for its high density of healthcare facilities. Private practitioners in the area were interviewed using a structured interview schedule. Based on a 1-year recall period, the schedule covered different aspects of the practitioners' HIV/AIDS management practices including diagnosis, treatment and referral. RESULTS: Of the 215 practitioners interviewed, 66% had tested and diagnosed HIV infection. Fifty-four per cent had been consulted by HIV-infected clients 'shopping' for alternative diagnoses or treatment. Overall, 75% of the respondents had been consulted by HIV-infected clients for treatment. Of these, 14% had prescribed antiretroviral drugs, sometimes without adequate knowledge of the guidelines for their use. Other supportive and symptomatic treatments were also frequently prescribed. Private practitioners commonly referred HIV-infected clients for management to other private doctors, or to public hospitals. There were variations in respondents' practices by sex and system of medicine. CONCLUSION: Private practitioners are actively involved in diagnosing and managing patients with HIV/AIDS. Some of their management practices are inappropriate and need to be remedied. There are also concerns about gaps in the continuity of care of HIV-infected persons, for which networks between providers need to be strengthened. Public-private partnerships must be created to improve the flow of information to private practitioners, and Include them in the national health framework.

Delivery of didanosine from enteric-coated, sustained-release bioadhesive formulation.

The aim of our study is to assess the release characteristics, in vitro permeation, and stability of an enteric-coated, bioadhesive, sustained-release formulation of didanosine (ddI). Enteric-coated tablets of ddI, containing Polyox WSRN-303 and Methocel K4M, were prepared using hydroxypropylmethylcellulose phthalate (HPMCP 5.5). The enteric-coated formulation was resistant to dissolution in 0.1 N HCl solution but dissolved within 10 min (+/-2 min) in pH 7.4 phosphate buffered saline. The release profiles were linear with square root time. Stability studies indicate that the formulations were stable at 4 degrees C, room temperature, and 40 degrees C upon storage for 6 months. Polyox WSRN-303 tablets exhibited a higher ddI permeation ratio across live intestinal tissue compared with conventional tablets. Enteric-coated, sustained-release, bioadhesive tablets deliver ddI in small doses and at the same time prevent acid-induced degradation and hence hold a potential to improve ddI's oral bioavailability.