Optimizing Process Parameters for Controlled Drug Delivery: A Quality by Design (QbD) Approach in Naltrexone Microspheres.

The formulation of microspheres involves a complex manufacturing process with multiple steps. Identifying the appropriate process parameters to achieve the desired quality attributes poses a significant challenge. This study aims to optimize the critical process parameters (CPPs) involved in the preparation of naltrexone microspheres using a Quality by Design (QbD) methodology. Additionally, the research aims to assess the drug release profiles of these microspheres under both in vivo and in vitro conditions. Critical process parameters (CPPs) and critical quality attributes (CQAs) were identified, and a Box-Behnken design was utilized to delineate the design space, ensuring alignment with the desired Quality Target Product Profile (QTPP). The investigated CPPs comprised polymer concentration, aqueous phase ratio to organic phase ratio, and quench volume. The microspheres were fabricated using the oil-in-water emulsion solvent extraction technique. Analysis revealed that increased polymer concentration was correlated with decreased particle size, reduced quench volume resulted in decreased burst release, and a heightened aqueous phase ratio to organic phase ratio improved drug entrapment. Upon analyzing the results, an optimal formulation was determined. In conclusion, the study conducted in vivo drug release testing on both the commercially available innovator product and the optimized test product utilizing an animal model. The integration of in vitro dissolution data with in vivo assessments presents a holistic understanding of drug release dynamics. The QbD approach-based optimization of CPPs furnishes informed guidance for the development of generic pharmaceutical formulations.

Optimization of Variance Reduction Techniques used in EGSnrc Monte Carlo Codes.

Monte Carlo (MC) simulations are often used in calculations of radiation transport to enable accurate prediction of radiation-dose, even though the computation is relatively time-consuming. In a typical MC simulation, significant computation time is allocated to following non-important events. To address this issue, variance reduction techniques (VRTs) have been suggested for reducing the statistical variance for the same computation time. Among the available MC simulation codes, electron gamma shower (National Research Council of Canada) (EGSnrc) is a general-purpose coupled electron-photon transport code that also features an even-handed, rich set of VRTs. The most well-known VRTs are the photon splitting, Russian roulette (RR), and photon cross-section enhancement (XCSE) techniques. The objective of this work was to determine the optimal combination of VRTs that increases the simulation speed and the efficiency of simulation, without compromising its accuracy. Selection of VRTs was performed using EGSnrc MC User codes, such as cavity and egs_chamber, for simulating various ion chamber geometries using 6 MV photon beams and 1.25 MeV 60Co photon beams. The results show that the combination of XCSE and RR yields the highest efficiency for ion-chamber dose calculations inside a 30 cm × 30 cm × 30 cm water phantom. Hence, properly selecting a different VRT without altering the underlying physics increases the efficiency of MC simulations for ion-chamber dose calculation.

Determination and estimation of pharmacokinetic profile of caffeine in form of extract of green tea leaves and its analogy with synthetic form.

The aim of the study was to formulate and investigate the pharmacokinetic parameters for the tablets of herbal extract of caffeine with comparison to synthetic formulation. The tablets of the aqueous herbal extract of leaves of Camellia sinensis and synthetic caffeine were formulated by wet granulation technique. The HPLC and HPTLC were applied as analytical tools for estimation of caffeine. The batches of formulation (B1 to B7) were subjected for various pre and post-formulation studies. The pharmacokinetic of the batch B5 was assessed in rabbits, and the results were compared to synthetic batch B7. With the suitable pre and post-formulation results, the B5 showed in vitro release of 90.54% of caffeine at the end of 60 min. The release followed first order kinetics and the plot of Higuchi and Peppas confirms anomalous diffusion as the basic mechanism behind the release. B5 revealed non-significant mean C(max), t(1/2), and AUC of 1.88 µg/ml, 5.52 h and 9.67 µg.h/ml respectively compared to B7. The study highlights; no significant difference in the pharmacological effect of caffeine when administered in the form of extract. The administration of herbal extract can further provide the other health benefits lacked by synthetic caffeine.