Current Drug Therapy - Volume 16, Issue 1, 2021

Burn wound associated injury management is one of the major unresolved clinical concerns. Most of the drugs and dressing materials available in the market cause dose escalation and even exert side effects. Besides, a severe burn injury is susceptible to microbial infection that leads to the prolonged hospital stay, which ultimately causes a financial crisis to the victims. To get rid of this problem, researchers are being interested in developing such materials that are cost-effective, easily available and accelerate faster healing. Human amniotic membrane (AM) and various herbal extracts like curcumin are a potential source of burn wound healing. AM has various healing properties and is being used as the best burn wound dressing material for centuries. Similarly, curcumin has been proven as a faster dressing material for the treatment of burn injury. Since both AM and curcumin are a potential source of burn and wound healing, if a gel/agent could be formulated by mixing these two things, this combination may be a potential therapeutic strategy to treat burn wound healing.

Self-emulsifying drug delivery systems (SEDDS) include self-microemulsifying drug delivery system (SMEDDS) and self-nanoemulsifying drug delivery system (SNEDDS) whose major benefits are reduction of inter/intrasubject variability and food effect that results in a better pharmacological response of the drug. Oral intake of these formulations triggers the digestion process because of pancreatic lipase which emulsifies/digests the lipidic ingredients of the formulation leading to precipitation of the drug. As a tool to foresee in vivo medicament precipitation, in vitro lipolysis models are established. Biorelevant media play an important role to study the effect of in vitro lipolysis and food impact on the bioavailability of SEDDS formulations. It is vital to generate the composition of fluids for both fed and fasting conditions of gastric, small intestine and colon to investigate the impact of in vitro lipolysis and food on drug’s release behavior from the formulation. Fed/Fasted state simulated gastric fluid (Fe/FaSSGF), and Fed/Fasted state simulated gastric fluid (Fe/FaSSIF) (Phosphate buffers) are first-generation. While Fa/FeSSIF-V2 (maleate) are second- generation biorelevant media utilized for these studies. FaSSIF-V3 belongs to the thirdgeneration which differs from other generations in the composition and source of bile salts. With updates in physiological data, it is vital to incorporate changes in dissolution media composition to make it more biorelevant. This review paper mainly emphasized the compositions of biorelevant media of gastric and small intestine for both fed and fasting conditions. Besides, applications of biorelevant media to investigate the effect of in vitro lipolysis and food on SEDDS are discussed with some recent research reports.

Background: The pathological agent of Coronavirus disease 2019 (COVID-19) is a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has its origin in Wuhan, China, and spread to other provinces of China and subsequently to other countries resulting in a pandemic worldwide. The virus is extremely contagious and causes pneumonia and respiratory failure. Since its emergence, researchers around the world are trying to develop vaccines and find suitable drugs for the treatment of COVID-19. Objective: To give an overview of the various therapeutic agents for COVID-19 such as vaccines and drugs that are in preclinical stage or under different stages of clinical trials. Results: As per World Health Organization (WHO), there are 137 vaccines under development to date, out of which few vaccines have successfully completed preclinical studies and reached clinical trials. According to the present scenario, only one coronavirus vaccine (sputnik-V) has been approved by the Ministry of Health of the Russian Federation. Till date, there are no United States Food and Drug Administration (USFDA) approved drugs to treat COVID-19 patients. However, depending on patient’s condition, different drugs such as antiviral agents like Remdesivir, antimalarial drugs like Hydroxychloroquine, antibiotics like Azithromycin and corticosteroids like Dexamethasone are being applied and some of them have proved to be effective up to a certain extent. Conclusion: Although several vaccines for COVID-19 are under development and various drugs have been tried for its treatment, an ideal drug candidate or a vaccine is still lacking. Almost all the big pharmaceutical companies are associated with one or more research initiatives in order to develop vaccines and drugs. Many of them are going through clinical stages, expecting a positive outcome by the end of 2020.

Background: Oral cancer is the life threatening disease causing mortality. The majority of chemotherapeutic anticancer agents are toxic to healthy tissues, have poor bioavailability and affect the quality of life of the patients. Objective: The main challenge in the treatment of oral cancer is the effective and safe delivery of chemotherapeutic anticancer drugs. This present review deals with the recent advancement in the nanotechnologies and its probable applications in the oral cancer treatment. Methods: This review includes a gist of suitable literature. Results: Nanotechnology brings novel methodologies or modifications in current anticancer therapies to improve individual wellbeing and survival. Conclusion: Nanotechnology put forward the potential of increasing the efficacy of the therapy and targeted drug delivery, which in turn increase drug absorption and bioavailability at the site of tumour. Different nanocarriers include liposomes, polymeric nanoparticles, inorganic nanoparticles, combinational (polymeric- inorganic) nanoparticles, magnetic nanoparticles, nanolipids, hydrogels, dendrimers and polymeric micelles. This review confers development of new drug delivery approaches for effective therapeutic outcomes and abating the toxicity to healthy tissues.

Background: Controlled oral dosage forms have always been preferred for drugs with variable absorption, and short biological half life and frequent dosing. The prime goal with sustained release systems is to maintain uniform therapeutic blood levels for more extended periods of time. Interpenetrating networks (IPNs) have been evidenced as uniform sustained release systems. In the current study, polyvinyl alcohol (PVA) and locust bean gum (LBG) based IPNs were developed for the oral sustained release drug delivery of gliclazide (shows variable absorption). Methods: The IPNs were synthesized by emulsion cross-linking method using glutaraldehyde (GA) as a cross linking agent. Gliclazide is a potential second generation, and short-acting sulfonylurea oral hypoglycemic agent having a short biological half-life (2-4 h), variable absorption and poor oral bioavailability. Various batches of IPNs were formulated by varying LBG: PVA ratio and evaluated for percentage yield, drug entrapment efficiency (DEE), swelling properties and in vitro drug release studies. Further characterizations were done by Fourier Transform Infrared Spectroscopy (FTIR), C13 Solid state NMR, X-Ray diffraction study (XRD), Scanning electron microscopy (SEM), and Differential scanning microscopy (DSC) studies. Results: The percentage yield, drug entrapment and equilibrium swelling were observed to be dependent on PVA-LBG ratio and GA amount. Sustained release of drug was observed in all IPN formulations (approx 59 - 86% in 8 h in various batches) with variable release kinetics. SEM studies revealed the regular structures of IPNs. FTIR, XRD, C13 Solid state NMR and DSC studies proposed that drug was successfully incorporated into the formed IPNs. Conclusion: IPNs of LBG and PVA can be used as a promising carrier with uniform sustained release characteristics.

Background: Tuberculosis (TB) continues to be among the leading causes of high mortality among developing countries. Though a seemingly effective treatment regimen against TB is in place, there has been no significant improvement in the therapeutic rates. This is primarily owing to the high drug doses, their associated side-effects, and prolonged treatment regimen. Discontinuation of therapy due to the severe side effects of the drugs results in the progression of the infection to the more severe drug-resistant TB. Objectives: Reformulation of the current existing anti TB drugs into more efficient dosage forms could be an ideal way out. Nanoformulations have been known to mitigate the side effects of toxic, high-dose drugs. Hence, the current research work involves the formulation of Isoniazid (INH; a first-line anti TB molecule) loaded chitosan nanoparticles for pulmonary administration. Methods: INH loaded chitosan nanoparticles were prepared by ionic gelation method using an anionic crosslinker. Drug-excipient compatibility was evaluated using DSC and FT-IR. The formulation was optimized on the principles of Quality-by-Design using a full factorial design. Results: The obtained nanoparticles were spherical in shape having an average size of 620±10.97 nm and zeta potential +16.87±0.79 mV. Solid-state characterization revealed partial encapsulation and amorphization of INH into the nanoparticulate system. In vitro release study confirmed an extended release of INH from the system. In vitro cell line-based safety and efficacy studies revealed satisfactory results. Conclusion: The developed nanosystem is thus an efficient approach for antitubercular therapy.

Background: Asthma and Chronic Obstructive Pulmonary Diseases (COPD) are well known respiratory diseases affecting millions of people in India. In the market, various branded generics, as well as generic drugs, are available for their treatment and how much cost will be saved by utilizing generic medicine is still unclear among physicians. Thus, the main aim of the current investigation was to perform cost-minimization analysis of generic versus branded generic (high and low expensive) drugs and branded generic (high expensive) versus branded generic (least expensive) used in the Department of Pulmonary Medicine of Era Medical University, Lucknow for the treatment of asthma and COPD. Methods: The current index of medical stores (CIMS) was referred for the cost of branded drugs, whereas the cost of generic drugs was taken from the Jan Aushadi scheme of India 2016. The percentage of cost variation, particularly to Asthma and COPD regimens on substituting available generic drugs, was calculated using standard formula and costs were presented in Indian Rupees (as of 2019). Results: The maximum cost variation was found between the respules budesonide high expensive branded generic versus least expensive branded generic drugs and generic versus high expensive branded generic. In combination, the maximum cost variation was observed in the montelukast and levocetirizine combination. Conclusion: In conclusion, this study inferred that substituting generic antiasthmatics and COPD drugs can bring potential cost savings in patients.

Background: Boldine, is an aporphine alkaloid that possesses potent antioxidant activity. Despite having enormous potential, the clinical application of boldine was restricted because of its poor bioavailability attributed to its poor aqueous solubility and rapid clearance from the body. The drug phospholipid complexation techniques were frequently employed to overcome the limitation of low bioavailability of phytoconstituents/herbal extract. Objective: The boldine phospholipid complex (BOL-PC) formulation was developed for enhancing antioxidant potential of boldine by preparing its phospholipid complex. Methods: Boldine loaded phospholipid (BOL-PC) complex was prepared by refluxing followed by solvent evaporation method and subjected to various physicochemical and spectral analysis. Further, the in-vitro antioxidant activity was evaluated by DPPH free radical scavenging method. Results: The formation of the complex was confirmed by ¹H NMR and thermal analysis. SEM and PXRD revealed partial amorphization of drug in complex formed. The BOL-PC dissolution rate and solubility were significantly improved compared to the parent compound. The maximum % yield and % EE were found to be 95.92± 0.01732 and 95.89±0.3502 respectively in the optimized formulation (F3), which exhibited concentration-dependent antioxidant property. Conclusion: It was concluded from the study that the phospholipid complexation of boldine has better antioxidant potential and improved the solubility, dissolution profile which may facilitate its oral absorption and enhances its chances for clinical application.

Background: Gliclazide (GLZ) belongs to the second-generation of sulphonylureas; it is a drug of choice for the management of type II DM. It belongs to BCS Class II. The major site of drug absorption for GLZ is the stomach; it displays variation in the drug absorption rate and bioavailability due to the shorter gastric retention time. The floating mechanism gets affected when the gastric fluid level is not sufficiently higher, which ultimately obstructs the floating behavior, which is the major limitation of reported formulations. This limitation can be overcome by folding the film into the capsule shell dissolved in the gastric fluid and the film swells/expands to dimensions higher than pylorus sphincter (12mm), thus preventing its evacuation. Objective: The study aims to explore the floating mechanism in the design of films along with a tendency to expand by swelling and unfolding by utilizing a mixture of hydrophilic and hydrophobic polymer to achieve the controlled drug delivery and prolonged gastric retention of drug. Methods: The gastroretentive floating films were formulated by the solvent casting technique using 3² full factorial designs and subjected to in vitro evaluation parameters, drug-excipient compatibility, Xray diffraction and accelerated stability study. Results: The pre-formulation study established the purity and identification of a drug. FTIR study confirmed no drug excipient interaction. F3, F6, and F9 were optimized based on in vitro floating characteristics, swelling/expanding ability, and unfolding time. All developed formulations were unfolded within 14-22 min after capsule disintegration. The F3 was selected as the final formulation as its ability to control the release of the drug for 24 hrs followed by zero-order kinetics having super case 2 transport. XRD confirmed the amorphousness of the drug within the formulation. The stability study results revealed that the formulation was quite stable at extreme storage conditions. Conclusion: The developed novel formulation has good potential for the effective management and treatment of diabetes mellitus.

Background: Gliclazide assimilation rate from the gastrointestinal (GI) tract is slow and inconstant, which may be either due to poor dissolution or poor permeability of the drug across the GI membrane. Objective: The present investigation deals with the formulation of floating-mucoadhesive tablets of gliclazide for oral administration using the central composite design by direct compression technique, using HPMC K4M and Carbopol 934 as release controlling polymers and sodium bicarbonate as an effervescent agent. Methods: Central composite design was employed to quantify the effect of three factorsconcentration of HPMC K4M (X1), the concentration of Carbopol 934 (X2), and concentration of sodium bicarbonate (X3) on floating lag time, drug release and mucoadhesive time of the formulation. Results: The results revealed that floating lag time decreases with a rise in the concentration of sodium bicarbonate, drug release was highest at low levels of HPMC and Carbopol and mucoadhesive time was highest at a high level of Carbopol. Conclusion: The optimized batch (F-7) shows a mucoadhesive time of 23 minutes 27 seconds, floating lag time of 22 seconds and in vitro cumulative percentage of drug release 86.73 % in 10h. From the investigation, it can be summarized that the gastro-retentive drug delivery can be utilized to enhance bioavailability and gastric residence time of the drugs.