Troikaa Pharmaceuticals Ltd.

This investigation aimed to design, develop, and optimize intranasal nanoemulsion for brain targeted delivery of lurasidone hydrochloride for the management and treatment of schizophrenia. The design of experiment supported optimization of high-pressure homogenization (HPH) process was executed for the manufacturing of lurasidone loaded nanoemulsion. The nanoemulsion comprising of lurasidone hydrochloride (10 mg/mL), 20% Oil_mix, 25% surfactant and, 55% aqueous phase (w/w) was processed with HPH at optimized conditions to get droplet size in the nano range. The droplet size of optimized nanoemulsion was found to be 48.07 ± 3.29 nm with a polydispersity index of 0.31 ± 0.01. The optimized translucent nanoemulsion (% transmittance of 88.56 ± 2.47) was found to be non-toxic to sheep nasal mucosa and stable for six months. The results of ex vivo diffusion study revealed the improvement in drug diffused by mucoadhesive nanoemulsion (MLNE) (1.41 × 10^-4 ± 1.11 × 10^-5 cm²/min) as compared to the solution (1.15 × 10^-4 ± 1.35 × 10^-5 cm²/min). The results of pharmacodynamic studies in mice uncover the highest inhibition of compulsive behavior (64.63%) and spontaneous locomotor activity (60.87%) shown by MLNE. This may be due to increased bioavailability in a brain, and possibly confirms the potential of nanoemulsion in targeting the brain through nasal route in the treatment of schizophrenia.

Gliclazide is a second‐generation sulphonylurea drug widely used in the treatment of type 2 diabetes. However, there is no single report to describe the population pharmacokinetics of gliclazide in animal models. This study was aimed to evaluate the population pharmacokinetics (PK) of gliclazide in normal and alloxan‐induced diabetic rabbits using nonlinear mixed effects modeling. A total of 90 New Zealand white rabbits were administered with three doses (4.13, 8.27 and 16.53 mg/kg b.wt) of gliclazide by an oral route. Blood samples were collected up to 24 hr and the gliclazide concentrations in rabbit were determined using the HPLC method. The non‐compartmental and classical compartmental PK analyses were performed using Phoenix WinNonlin. Population PK analysis of gliclazide was performed using nonlinear mixed‐effects model software NONMEM and Phoenix NLME considering the weight, age, sex, health and dose as covariates. The final population values for clearance (CL), volume of distribution (V) and the absorption rate constant (ka) were 5270 ml/hr, 55700 ml and 0.708 hr−1, respectively. The inter‐individual variability in gliclazide CL, V and ka was 16.3%, 14.9% and 26.5%, respectively. There was no significant difference between NONMEM and Phoenix NLME pharmacokinetic results. The visual predictive check and bootstrap analysis confirmed the predictive ability, model stability and precision of the parameter estimates from this model. This population PK model demonstrated that gliclazide pharmacokinetics is best described by one‐compartment model with first‐order absorption in rabbits. Body weight is a covariate that significantly influences gliclazide kinetic disposition in rabbits.

To compare the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) and oral morphine in Indian patients with breakthrough episodes of cancer pain.

In this randomized, open label, active controlled, clinical study, total 186 patients who regularly experienced 1-4 episodes of breakthrough cancer pain (BTCP) daily, over the persistent pain controlled by taking oral morphine 60 mg/day or its equivalent were randomized to receive either OTFC 200 mcg or oral morphine 10 mg for the treatment of BTCP for 3 days. Improvement in pain as determined by numerical rating scale (NRS) at 5, 15, 30, and 60 minutes of drug administration and percentage of BTCP episodes showing reduction in pain intensity by >33% at 15 minutes were primary efficacy endpoints. Secondary efficacy endpoints were requirement for rescue analgesia and global assessment by physician and patient. Data of both treatment groups were analysed by appropriate statistical test using software, STATISTICA, version 11.

Patients treated with OTFC experienced significantly greater improvement in pain intensity of breakthrough episodes compared to those treated with oral morphine at all assessment time points (P < 0.0001). 56% of breakthrough pain episodes treated with OTFC showed a greater than 33% reduction in pain intensity from baseline at 15 minutes compared to 39% episodes treated with oral morphine (P < 0.0001). Patient's and physician's global assessment favoured OTFC than oral morphine (P < 0.0001). Requirement of rescue analgesia in both the study groups was similar (P > 0.05). Both study drugs were well tolerated.

OTFC was found to provide faster onset of analgesic effect than immediate release oral morphine in management of breakthrough cancer pain.