Drug Delivery Letters - Volume 14, Issue 2, 2024

Background: In the era of pharmaceutical research and development, the most challenging aspect is to enhance the physicochemical properties of drugs. Hot Melt Extrusion (HME) is a solvent-free, one-step, continuous, scalable, and industrially feasible method for developing pharmaceutical co-crystals. Co-crystallization, as a technique, has gained significant attention for its potential to modify various physicochemical properties of drugs like solubility, stability, compressibility, permeability, taste masking, and therapeutic efficacy. Methods: We determine the characteristic features of HME and explore published literature using the keywords, HME, co-crystals, and PAT, in databases, such as PubMed, Google Scholar, ScienceDirect, and Research Gate. Results: The present review embarks on a detailed journey through the multifaceted domain of HME and its pivotal role in co-crystal development. The process parameters, such as temperature, extruder type, screw configuration, screw speed, and feed rate, are involved in determining the characteristics of the co-crystals produced. Additionally, the review explores the role of materials, including Active Pharmaceutical Ingredients (APIs), plasticizers, polymers, and other pharmaceutical aids, underlining their impact on co-crystal development. The existing literature on HME and its application for pharmaceutical co-crystal production is comprehensively surveyed. Conclusion: The review highlights the utility of Process Analytical Technology (PAT) in realtime process control. The role of HME in the future of pharmaceutical co-crystal development is discussed, making this review essential for researchers and industry professionals alike.

All the standard anti-tubercular drugs, well established as standard therapy, are preferentially available in formulations compliant with the young adult population. However, their use in the paediatric and geriatric populations is confronted with issues, such as a high likelihood of incorrect dose administration due to practices like dosage form fracture and splitting. This may lead to drug resistance due to misuse and in-accurate dosage administration, the most dreaded and difficult-to-treat stage of tuberculosis. Poor patient compliance and adherence are major issues with the conventional line of therapy. This burden may be more significant in resource-constrained settings, necessitating the creation of simple formulations that are both geriatric and child-friendly. An extensive literature survey has been conducted in this study using databases of Google Scholar, PubMed, and Research Gate, with a focus on specific research works on oro-dispersible films, tablets, and wafer technology loaded with anti-tuberculosis drugs from 2022 to 2010. Mouth dissolving formulation technology is a very novel approach in the arena of tuberculosis therapy. This may pave the way for future researchers to develop different mouth dissolving formulations to treat both pulmonary and extra-tuberculosis. This review paper has summarized all the formulation approaches alongside the present state of the art in tuberculosis therapy using mouth dissolving formulations.

Nitrofurantoin is an antimicrobial drug, highly effective in the treatment of critical or chronic bacterial infections of the urinary tract, and hence, it is the first line choice of drug for the treatment of urinary tract infections (UTI). Although the molecule is legacy in nature, there are many challenges in terms of drug product formulation and efficacy thereof. The authors are mainly focused in this literature review on, but not limited to, understanding the molecule in terms of physico-chemical properties of the drug, pharmacokinetics and pharmacodynamics, approved and withdrawn formulations, challenges concerning drug formulation, the cause of drug shortage in the market, improvement areas in terms of formulation and its therapeutic effectiveness. The authors found during their widespread review that the major challenge in the existing conventional drug delivery system of nitrofurantoin is the fluctuation of plasma concentration owing to its variability in drug absorption. Further, they understood that the variability in absorption is due to inherent variability in particle size distribution. Based on the findings, authors also explored the possibilities to deliver the drug in novel drug delivery systems such as nano self-emulsifying emulsions, nanoemulsions and multiple emulsions where the drug can be presented in soluble form and hence the variability in absorption and fluctuation in plasma concentration of drug can be avoided and described briefly the salient features of each drug delivery in this review.

Background: In the current scenario, most of the population affected by neurogenerative disorders like Alzheimer's, Parkinson's, Huntington's, etc., exist among the 10% population 65 years of age group. Neurodegenerative diseases are characterised as chronic and progressive disorders that occur due to the degeneration of neurons. Baicalein is a flavonoid glycoside derived from the roots of Scutellaria baicalensis. Earlier research suggested that it could be used to treat neurodegenerative illnesses. Baicalein, which was selected for the current study, was designed into a solid lipid nanoparticle (SLN) formulation. The SLNs have low permeability across BBB and are delivered by the non-invasive route, i.e., through nasal delivery. The In-silico docking studies were performed to examine and compare the binding affinity of Baicalein to already established drugs on the two most viable targets of Alzheimer's disease, i.e., Beta- secretase and Acetylcholinesterase. Objectives: The current work is to formulate and evaluate the Baicalein-loaded SLN for neurodegenerative disorders via a non-invasive route. Methods: Baicalein loaded SLN was developed by solvent emulsification diffusion method, and formulation is characterised by using different parameters such as particle size analysis, zeta potential, scanning electron microscope, transverse electron microscope, X-ray diffraction, Differential scanning calorimetric, Fourier transforms -infrared radiations, drug entrapment, in-vitro drug release and in-silico docking studies. Results: The particle size of Baicalein-loaded SLN was 755.2 ± 0.48 nm, the Polydispersity index was 0.06, and the zeta potential was -32.5 ± 0.36 mV. The drug entrapment and loading efficiency of the optimised formulation were found to be 94% ± 0.653 and 18.2% ± 0.553, respectively. Optimised formulation shows 84.6% ± 0.3% of drug release within 30 minutes, which demonstrates the sustained release of the drug. Conclusion: Baicalein-loaded SLN is formulated and evaluated for the treatment of neurodegenerative disorders. SLN is an approach to overcome the challenge of bypassing the BBB by administering the drug via an intranasal route. Hence, when analysed together with the results of Baicalein-loaded SLN and in-silico studies, it was correlated that Baicalein proved to have a targeted moiety for neurodegeneration.

Background: Schizophrenia is a chronic disease with acute psychotic symptoms, which is having frequent recurrence. Paliperidone palmitate (PP) is a second-generation antipsychotic drug to treat schizophrenia. Aims: The aim of the study was to prepare lyophilized nanoemulsifying drug delivery system (NEDDS) of paliperidone (PD). Objectives: The primary objective of the current research work was to develop a lyophilized nanoemulsifying drug delivery system (NEDDS) of paliperidone (PD) to improve its oral bioavailability and stability. Methods: Optimization using D-Optimal Mixture Design DMD) was conducted, and optimized NEDDS was further lyophilized to improve stability. The lyophilized optimized NEDDS was further evaluated for biopharmaceutical evaluation. Results: A saturation solubility study revealed Peceol, Tween 80, and Plurol Olique CC497 as suitable candidates for oil, surfactant, and co-surfactant, respectively. Optimized NEDDS of PD showed mean globule size (MGS) of 185 nm, PDI of 0.27 and cumulative % drug release within 15 min Q15 of 86.6%. Lyophilized optimized NEDDS was found to have no significant change in quality attributes within the stability study period. A pharmacokinetic study revealed more than two-fold increases in bioavailability for lyophilized optimized NEDDS. Conclusion: Hence, lyophilized NEDDS of PD can be used as an effective approach for the improvement of oral bioavailability and stability.