Current Drug Therapy - Volume 16, Issue 5, 2021

Stem cells are the unique cells in the body which have the capability to divide continuously and differentiate into various other kinds of cells and tissues. This work represents the issues and challenges in the stem cells and stem cells-based products regulations and compares the related guidelines in India, the USA, and the EU. In India, stem cells (SCs) and stem cells-based products (SCBP) are considered as ‘drugs’ as per the recent guidelines and amendments in the Indian Drugs and Cosmetics Act with a view to streamline the regulatory framework for advanced research. The United States Food and Drug Administration (USFDA) and the Centre for Biologics Evaluation and Research (CBER) in America regulate stem cells and stem cell therapies-based products. European regulation 1394/2007 was issued in 2008, which lays down the legal framework for cell- derived medicinal products in Europe. In the present review, India, USA and EU guidelines have been compared and critically evaluated. After the comparison of the drug approval process in India, the USA and the EU, it was found that India and the USA both have a single registration process for the approval of the drug products, while the EU has multiple processes. The product approval time is more in the USA. EU charges more fees compared to the other countries. Previously, India was following paper CTD formats, but now India is following eCTD, which is also followed by US and EU countries.

Background: Executing the centralization of medication in the foundational flow for approaching their pharmacological has necessitated studying a vital parameter, i.e. solubility reaction. The poor water dissolvability has an impact on medication adequacy and, consequently, owned poor drugs bioavailability. Aim: The aim of this study is to attain the convergence of medication in an introductory course, a significant parameter, i.e. solvency, has been executed for the pharmacological reactions. On account of revolution and advancement, there is a diversity of new medications, and their subordinates are approachable. Over 40% of lipophilic medication up-and-comers neglect to achieve because of poor bioavailability even though these medications have potential pharmacodynamics activities. Due to high market requirements, lipophilic medication has accomplished the relevant pharmacological activity. Consequently, most strategies are streamlined to improve fluid solvency to upgrade proficiency and lessen the reactions for specific medications. Objectives: The process of hydrotropic solubilization has persisted a novel and promising methodology to improve the solvency of drugs with poor water solvency by ascending the dissolvability to many folds with the involvement of hydrotropes, i.e. Niacinamide, Urea, sodium benzoate, sodium citrate, and so on. The potentiality of hydrotropic solubilization counts on the balance among hydrophobic and hydrophilic parts of hydrotropes. Hence, advancement in hydrotropic updated visualized in novel drug delivery systems and their mechanism of compatibilities and biocompatibilities. Novelty is also reprinted in its usefulness as an extraction agent for bio-active compounds to increase the rate of heterogeneous reactions and in a green synthesis for a substrate. Conclusion: This review focuses on practice utilized for solubility management of drugs with poor solvency, its unmet needs, utilizing the artificial machine learning in the prediction of hydrotropeenhanced solubilization of drugs, practical applicability in drug delivery, interpreted kinetic involved, and various associated mechanisms.

Background: A combination of Glimepiride and Boswellia serrata extract reduces neuropathic diabetic complications by reducing the peroxidase level and improving the antioxidant level. The hybrid liquisolid method includes a combination of two methods, kneading and the liquisolid method, to enhance the drug’s in-vitro performance. Objective: The objective of this study was to enhance the in-vitro performance of antidiabetics drugs. Methods: Tablets involving a fixed-dose combination of Glimepiride and Boswellia serrata extract were formulated by kneading method followed by liquisolid method. Screening of non-volatile solvents, carriers, and coating materials was carried out. The experiment was designed to optimize the formulation and the obtained model was validated concerning the design of the experiment. 3 level 2 factorial (32) design was applied by using Design expert software 11. Various pre-compression parameters were assessed to check the quality of the formulation. Results: Screening of excipients for kneading method, including Glimepiride with PVP K 30 (5%), and Boswellia serrata extract with Poloxamer 188 (13%), provided optimum drug release. For the liquisolid method, propylene glycol:PEG 400: Tween 80 (1:2:4) ratio for Glimepiride and PEG 400: Tween 80 (1:3) ratio for Boswellia serrata extract were selected. Common carrier and coating material for both drugs were selected to improve the in-vitro performance of the drug. Conclusion: This study enables an overall understanding of the impact of excipients on the quality of formulation, which may provide critical knowledge for the implementation of liquisolid systems.

Background: Difficulty in swallowing tablet dosage form is common among all ages people, especially old and pediatrics. Fast dissolving oral films (FDOFs) may represent an innovative dosage type that settles the issue of gulping and supply fast onset of action. Objective: The objective of the present investigation was to increase the solubility of poorly soluble Glipizide (BCS Class II) by solid dispersion technique and develop its FDOFs. Methods: A solvent evaporation process was used to make a solid dispersion of the Glipizide. The saturation solubility of glipizide and its solid dispersion was determined in a different solvent. For the film preparation, solvent casting method was chosen. The excipients were selected based on pre-formulation data. The composition of the film was optimized based on a trial-and-error basis using different concentrations of plasticizer. The average weight, thickness, disintegration time, tensile strength, surface pH, folding endurance, drug content, and in-vitro dissolution analysis of the films were all taken into consideration. Results: There was no incompatibility between drug / solid dispersion and the excipients. The solid dispersion of the glipizide showed improved solubility by almost 10 folds. Many of the formulated films disintegrated in less than 30 seconds. At the end of 5 minutes, the optimized film had released more than 90% of the compound. The prepared films were found to be stable at room temperature. Conclusion: The solubility of Glipizide was improved successfully by solubilization technique using soluplus. The FDOFs of the glipizide were successfully formulated using pullulan as polymer.

Background: Tetrahydrocurcumin is a hydrogenated active metabolite of curcumin that exhibits similar pharmacological effects to curcumin. However, its hydrophobic nature has limited its aqueous solubility and bioavailability. By incorporating the tetrahydrocurcumin into β-cyclodextrin, its physiochemical property can be improved. Objective: To develop a chitosan composite loaded with tetrahydrocurcumin inclusive complex, characterize the developed composites, and evaluate its effectiveness on cancer cells. Methods: Tetrahydrocurcumin was formulated into an inclusive complex with β-cyclodextrin in the ratio of 1:2 (Tetrahydrocurcumin: β-cyclodextrin). The tetrahydrocurcumin inclusive complex loaded chitosan particles (THC IC-loaded CPs) were prepared using ionic gelation and later characterized using FTIR. Cytotoxicity of THC IC-loaded CPs in human colon cancer cells, Caco-2 cells, was examined using RTCA xCELLigence technology. The uptake of these particles by Caco-2 cells was also evaluated via fluorescing microscopy. Results: FTIR results confirmed the formation of the tetrahydrocurcumin inclusive complex and the loading of this complex into chitosan composites. The cytotoxic effect of THC IC-loaded CPs showed a dose-dependent relationship, and the IC50 found was 1.117mM and 0.959mM after 48 and 72 hours, respectively. THC IC-loaded CPs showed an immediate uptake by CaCo-2 cells, and the maximum uptake was observed after 1 hour of incubation. Conclusion: This study showed that THC IC-loaded CPs is a potential drug carrier to deliver tetrahydrocurcumin into cancer cells and able to produce a cytotoxic effect on cancer cells.

Objectives: Multiple sclerosis (MS) is a long-lasting demyelinating inflammatory disease of the central nervous system (CNS). It has been shown that brain tissue in MS is exposed to oxidative stress during the disease period. Silymarin, a plant-derived flavonoid, can be extracted from Silybum marianum. The current experiment aimed to explore the effects of silibinin and especially nano-silibinin on neurobehavioral activity and biochemical antioxidant parameters in the cuprizone model of demyelination in mice for the first time. Methods: Demyelination was induced in mice by oral consumption of cuprizone 0.4%w/w for one week and then 0.2%w/w for four weeks. Treatment was performed with silibinin or nano-silibinin (70mg/kg body weight) for four weeks at the same time with cuprizone 0.2%w/w. After neurobehavioral tests (rotarod, tail flick, and open field), biochemical antioxidant parameters (glutathione level, superoxide dismutase activity, lipid peroxidation products, and total antioxidant capacity) were evaluated. Results: In this experiment, behavioral tests (rotarod and open field) displayed improvement in movement dysfunction using silibinin or nano-silibinin. Furthermore, silibinin and more efficiently nano-silibinin increased antioxidant parameters, such as superoxide dismutase (SOD) and glutathione (GSH) and total antioxidant capacity (TAC), and decreased lipid peroxidation. Conclusion: These data suggest that silibinin and nano-silibinin can improve movements in the cuprizone model of demyelination. Moreover, they may prevent cuprizone-induced oxidative stress. In conclusion, silibinin and more effectively, nano-silibinin, may exhibit therapeutic features in MS disease.

Background: Fixed drug eruption (FDE) is an erythematous cutaneous patch caused by certain drugs through activation of immunologic reactions in the body. The onset of FDE is 30 minutes to 8 hours and is estimated to occur in upto 16-21% of all cutaneous reactions. The irrational combination of fluoroquinolones and nitroimidazole is the most prescribed drug for diarrhea in India, and the drug is found to cause FDE either individually or in combination. Cross sensitivity is the major issue associated with Fluoroquinolones and nitroimidazole. Case Report: Our case is of a 45-year-old male who developed FDE due to a combination product of ofloxacin and ornidazole with past FDE history due to a combination product of norfloxacin and tinidazole. The patient presented with erythematous patches all over the body, swollen lips, mucosal erosion over the buccal cavity, and glans penis. Discussion: The patient was successively treated after the withdrawal of the culprit drug with oral Antihistamines, corticosteroids, and other topical creams and gels, which correlates with the standard management of FDE. Conclusion: Proper prescribing knowledge, documentation of drug allergies, and educating patient about allergic reaction play vital role to prevent future drug related problems.