Study of adverse drug reactions to antiretroviral therapy in a tertiary care hospital, Tirupati.

PURPOSE: Human immunodeficiency virus-infected patients do not adhere to their antiretroviral therapy (ART) due to adverse effects of drugs. The continuous monitoring of adverse drug reactions (ADRs) may ensure the safe use of drugs in patients. Hence, a retrospective analysis was carried out to assess the ADRs pattern, causality, and severity associated with various antiretroviral drug regimens in patients receiving ART. MATERIALS AND METHODS: A retrospective, analytical study was carried out at ART nodal center in Sri Venkateswara Ramnarain Ruia Government General Hospital, Tirupati. Data were collected by spontaneous reporting of health-care professionals from ART centers using Suspected ADR Reporting Forms of Indian Pharmacopoeia Commission to record the ADRs occurred in the patients who underwent treatment from December 2015 to November 2016. A total of 299 ADR reports were collected during the study period. The causality and severity of the reported ADRs were assessed using suitable scales. RESULTS: From a total of 299 ADR reports, females (63.81%) experienced higher ADRs than males (36.12%). The highest number of ADRs was reported to zidovudine/lamivudine/nevirapine (ZLN) regimen (76.92%) than tenofovir/lamivudine/efavirenz (TLE) regimen (23.07%). Cutaneous reactions were higher (34.34%) among patients receiving ZLN therapy, and drowsiness (53.62%) was the most common ADR in patients receiving TLE regimen. According to the World Health Organization causality assessment scale, most of the ADRs were possible (75.92%). On the assessment of Modified Hartwig and Siegel Severity Scale, 55.09% of ADRs were moderate. CONCLUSION: The study showed an increased incidence of ADRs to ART which calls for efficient pharmacovigilance systems to improve patient care and drug safety.

Formulation and biopharmaceutical evaluation of risperidone-loaded chitosan nanoparticles for intranasal delivery.

Objective: High lipophilicity and extensive hepatic metabolism limits the oral application of risperidone in the treatment of CNS disorders. In order address this limitation, risperidone (RS) loaded chitosan nanoparticles (CS-NPs) were processed for intranasal administration in the management of schizophrenia. Methods: RS loaded CS-NPs were prepared by ionic gelation of chitosan with tripolyphosphate and stabilized by tween 80/ poloxamer 188. The CS-NPs were characterized by FTIR, DSC, particle size, zeta potential and surface morphology. Entrapment efficiency, mucoadhesive strength, in vitro drug release, and release kinetics of CS-NPs were evaluated. Pharmacokinetics and pharmacodynamics of RS loaded CS-NPs were studied using Wistar rats. Stereotypy behavior and swimming normalization tests were conducted in amphetamine induced psychosis in animals. Results: Risperidone nanoparticles (RP12) were produced with an average size of 86 nm, polydispersity index of 0.287, zeta potential of +36.6 mV, mucoadhesion of 68.9% and entrapment efficiency of 77.96%. CS-NPs released the RS in controlled manner with Fickian diffusion mode. Maximum concentration of RS in plasma was 1240 ng/ml at 4 h for RP12, and 403.8 ng/ml at 2 h for RS sample. RS loaded CS-NPs significantly reduced the stereotypy score in experimental animals that indicated the efficiency of CS-NPs in delivery of RS at brain tissues and moreover amphetamine effect was reversed. Thus, RS loaded CS-NPs proved as potential delivery systems against induced psychotic disorders. Conclusion: Risperidone loaded chitosan nanoparticles were effective against schizophrenia via intranasal route.

Biopharmaceutical Potential of Selegiline Loaded Chitosan Nanoparticles in the Management of Parkinson's Disease.

BACKGROUND: Selegiline hydrochloride, a hydrophilic anti-Parkinson' moiety, undergoes extensive first-pass metabolism and has low bioavailability. A process to obtain of selegiline (SH) loaded chitosan nanoparticles was attempted to circumvent the above problem, through intranasal delivery. METHODS: SH loaded polymeric nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate, and stabilized by tween 80/ poloxamer 188. The resulting nanoparticles (NPs) were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, entrapment efficiency, particle size, zeta potential and surface morphology by scanning electron microscopy. Further, they were schematically evaluated for mucoadhesive strength, in-vitro drug release, release kinetics, pharmacokinetics, catalepsy, akinesia, in-vivo lipid peroxidation, nitrite levels, glutathione, catalase enzyme levels in brain and physicochemical stability parameters. RESULTS: Selegiline nanoparticles (SP18) produced were in size of 63.1 nm, polydispersity index of 0.201, zeta potential of +35.2 mV, mucoadhesion of 65.4% and entrapment efficiency of 74.77%. Selegiline showed biphasic release from nanoparticles, over a period of 36 h, with Fickian diffusion controlled release profile. Maximum concentration of SH in plasma was recognized as 52.71 ng/ml at 2 h for SP18, 20.09 ng/ml at 1 h for marketed formulation, and 21.69 ng/ ml for drug solution. SH loaded NPs showed a reversive effect in catalepsy and akinesia behaviour. This effect was especially pronounced in rats receiving SH loaded CS-NPs. Significant decrease in lipid peroxidation and nitrite concentration; increase in reduced glutathione and catalase enzyme levels were obtained due to antioxidant characteristics of SH, which turned to be useful to treat Parkinson's disease. CONCLUSION: Selegiline loaded chitosan nanoparticles form an effective non-invasive drug delivery system of direct nose to brain targeting in Parkinson's disease.