Experience of patients on methadone maintenance treatment receiving take-home methadone doses during COVID-19 pandemic: A multi-site study from India.

BACKGROUND: Methadone take-home doses for opioid dependence treatment are strictly regulated due to diversion and overdose concerns, so patients must visit the clinic daily for dispensing. This was also done in India until the COVID-19 pandemic, when lockdown restriction compelled take- home dispensing of methadone. This study examined experience of patients who received take- home methadone during COVID-19 pandemic in India. METHODS: Observational, cross-sectional design. We contacted all consenting methadone centres in India during the lockdown and selected those that provided take-home doses for the study. Patients who received daily methadone before the lockdown and take-home doses after were interviewed using a study-specific questionnaire. RESULTS: The study had 210 participants. Take-home methadone was dispensed for 2.5 days on average in each dispensing. When taking methadone at home, 3.3% split their dose 25% took less than the prescribed dose to save it for a rainy days, and 3.3% reported an overdose episode. Adherence improved in 58.6% participants after take-home methadone. Participants perceived many benefits from take-home methadone such as reduced hospital visits and travel time to collect methadone, improvement in work, and financial savings. About 54.3% participants reported storing their take-home doses safely, and 1.9% reported that their family consumed methadone by mistake. CONCLUSIONS: Take-home methadone was found to be beneficial to most participants in terms of time saved and improved productivity. Preconceived concerns of providing take-home methadone in terms of its overdose, diversion, or accidental ingestion by others are not commonly seen when individuals are provided take-home doses of methadone.

Development of Carbamazepine Nanostructured Lipid Carrier Loaded Thermosensitive Gel for Intranasal Delivery.

Purpose: The present research work was designed to formulate and evaluate carbamazepine (CBZ) loaded nanostructured lipid carrier (NLC) based in-situ gel for nasal delivery. Methods: The NLC formulation of CBZ was prepared by microemulsion technique followed by probe sonication and evaluated for particle size, zeta potential, entrapment efficiency and in vitro drug diffusion. NLC formulation was incorporated into in-situ gelling formulation using poloxamer 407 (P407), poloxamer 188 (P188) and mucoadhesive polymer. The effect of concentration of poloxamer 188 (X1 ), type of mucoadhesive polymer (X2 ) and concentration of mucoadhesive polymer (X3 ) on gelling temperature (Y1 ) and drug diffusion after 8 h (Y2 ) was studied using Box-Behnken design. In vivo anticonvulsant activity of optimized formulation was studied in Wistar rats by maximal electro-convulsion model (MES). Results: The optimized CBZ NLC formulation, with 20% drug loading, 0.5:1 as Precirol:Capmul MCM ratio as lipid phase and 1:3 as Lipid:Smix ratio, resulted in 89.73±0.2% drug entrapment, 55.95±1.09% of drug diffusion after 8 h, particle size of 132.8 nm with polydispersity index of 0.302 and zeta potential of -29.2±6.1 mV. The in-situ gel formulation with 20% P407, 5% P188 and 0.2% chitosan was optimized and demonstrated excellent gelling ability, gelling temperature in the range of 30 to 35°C, 42.46% of drug diffusion in 8 h by Fickian diffusion mechanism and 31.34±0.76% of drug permeation through sheep nasal mucosa. In vitro anticonvulsant activity in MES model in rat demonstrated significant efficacy (71.95% protection against seizure in extension phase) as compared to plain in-situ nasal gel (50.26% protection against seizure in extension phase). Conclusion: NLC based in-situ gelling formulation demonstrated its potential for nasal delivery of CBZ with improved anticonvulsant activity.

Formulation and Optimization of Topical Solid Lipid Nanoparticles based Gel of Dapsone Using Design of Experiment.

OBJECTIVE: The present research work was designed to formulate and evaluate solid lipid nanoparticles (SLN) loaded gel of Dapsone (DS). An attempt was made to develop topical gel with better skin permeation rate. METHOD: The SLN formulations of DS were prepared by microemulsion technique and evaluated for its in vitro characteristics. The effect of DS concentration in lipid phase (X1), Gelucire:Precirol ratio (X2) and lipid:Smix ratio (X3) on entrapment efficiency (Y1) and drug release (Y2) from SLN was studied using Box-Behnken design. The result of dependent variables was used to generate polynomial equations and the surface response and counterplots. The optimized SLN formulation was incorporated into the gel using 1% carbopol-934 as a gelling agent. The SLN loaded gel was characterized for pH, viscosity, percent drug content, in vitro drug release and ex vivo permeation through rat skin. RESULTS: The optimized DS SLN formulation, with 20% drug loading, 0.5:1 as Gelucire : Precirol ratio in lipid phase and 1:3 as Lipid : Smix ratio, showed 95.64±0.2% drug entrapment, 61.1±0.6% of drug release after 8 h, particle size of 168.5 nm with polydispersity index of 0.335 and zeta potential of -16.8±6.1 mV. DS SLN gel demonstrated biphasic release pattern with greater drug permeation through rat skin (Jss, 39.27±2.1 µg/cm2/hr) as compared to plain DS gel (Jss, 22.64±1.8 µg/cm2/hr). CONCLUSION: The present study demonstrated DS SLN gel as a possible alternative to a conventional topical formulation for the treatment of acne.