Current Drug Therapy - Volume 15, Issue 5, 2020

Coronavirus (CoV) is an enveloped positive-sense RNA virus. Coronavirus disease 2019 (COVID-19) is an acute respiratory disease, induced by a new type of coronavirus, SARS-CoV-2. COVID-19 has originated in China and spread quickly all over the world. WHO acknowledged the outbreak of a global pandemic on March 11, 2020. The spread of COVID-19 signified a big threat to social life, the economy, and public health. As of April 14, 2020, WHO reported a total of 1,812,734 confirmed cases of COVID-19 and 113,675 (6.27 %) deaths throughout the world. Numerous nations around the globe took assorted measures because of the danger of SARS-CoV-2 and created wide-ranging preventive approaches. No particular drug or vaccines/antibodies are yet accessible for the treatment of this unforeseen and lethal illness. The pandemic has brought about travel limitations and across the country lockdowns in most of the nations. The objective behind this article was to provide recent updates and well-authenticated information to the scientific community, health care personnel’s and common public about Coronavirus, their types, characteristic features, structure and origin, mode of transmission, pathogenesis, clinical symptoms, diagnostic methods, drug development approach, prevention and treatment of COVID-19.

Background: Different experimental methods have been used to induce diabetes in animals. There are a number of anti-diabetic drug loaded nano-formulations with high therapeutic value that are used to target diabetes with high therapeutic efficacy. Methods: From this review, various anti-hyperglycemic agents have been screened for their activity. The use of nano-formulation in diabetes treatment is considered due to the possibility of the incorporation of both hydrophilic and hydrophobic substances. Results: The clinical symptoms of diabetes are similar to those of hyperglycemia, glucosuria, polydipsia, polyphagia, and polyuria and these symptoms were produced in experimental animal models through various diabetogens. The treatment by using nano-formulation enhance the therapeutic efficacy due to an increase in high carrier capacity. Conclusion: The characteristic features of the disease and pathological changes during disease in small animals (rats or mice) are similar to that of human beings. The use of synthetic as well as herbal drugs have shown greater therapeutic efficacy by encapsulating into nano drug delivery system.

Background: Coronaviruses (CoVs), having enveloped RNA of positive strand, are mainly responsible for enzootic infections in mammals. The mortality of CoVs has been proved as they can cross the species barrier very easily and infect humans. Most recently, the outbreak of coronavirus induced COVID-19 emerged in the city of Wuhan, Hubei province of China and became the third highly pathogenic coronavirus infecting nearly 230 countries. Objective: To review the literature available about pathogenic Coronavirures with emphasis on pathogenesis of COVID-19, and passive antibody therapy prospective. Methods: This study reviewed relevant published literature to provide (1) structural similarities between coronaviruses and therapeutic methodologies used on SARS-CoV, MERS treatment which might help scientists in understanding novel COVID-19 infection, (2) understanding COVID-19 pathogenesis that may help in identification of appropriate therapeutic targets to develop specific and effective anti-viral drugs as well as immunizing agents against this novel emerging pathogen and (3) to discuss existing knowledge on the passive immune therapy against similar coronaviruses SARS-CoV and MERS-CoV with emphasis on COVID-19 pandemic treatment. Conclusion: COVID 19 coronavirus has shown resemblance to viral infections like SARS-CoV, MERS infection. Historically, it has been proved that the prevention of disease, when exposed to a biological system, is mainly a function of the immune response of that infected individual. To fight against these infections, passive antibody therapy is the only available countermeasure that could provide immediate immunity against infection. Passive antibody results in protection irrespective of the immune status of the host. This therapy can be advantageous in countering the biological attack, post exposure preventions, low toxicity and peculiar activity.

Nanoparticles (Np) are the 21st century material in supreme formulations due to their unique properties and design. In review, systematic discussion of the synthesis, characterization, bio-applications, and risks of AgNps (Silver Nanoparticles) especially highlighting anticancer activity envisaging mechanisms as well as therapeutic approaches for cancer. Ag-Nps mainly possess toxicological concern.

Benefits and Risk: AgNps have beneficial approaches for cancer treatment and angiogenesisrelated diseases like rheumatoid arthritis, atherosclerosis, diabetic psoriasis, retinopathy, endometriosis, and adiposity.

Ag-Nps induced cytotoxicity through oxidative stress by the ROS (Reactive Oxygen Species) generation could be measured as dependent on different properties, such as nanoparticle shape, size, agglomeration, concentration, and aggregation.

Results: The advancing nanotechnology-based therapy needs to be devised better, and it should offload the hitches of prevailing treatment approaches. Essential studies are required to explain the synergistic effect of two different cytotoxic agents.

Introduction: The infiltration of HIV into the brain alters the functions of the nervous system known as Neuro-AIDS. It leads to neuronal defects clinically manifested by motor and cognitive dysfunctions. Materials and Methods: Current antiretroviral therapy can prevent viral replication but cannot cure the disease completely. HAART-Highly active antiretroviral therapy is used for the treatment of HIV infection. Challenges in neuro-AIDS therapy are as shown in the graphical abstract. One of the challenges is latent viral reservoirs like the brain; which act as a sanctuary site for viruses. Nearly ~50% of HIV patients show neuropathological signs. Nervous system related disorders, including AIDS dementia, sensory neuropathy, and myelopathy have a 25% of prevalence in patients having access to a highly active combination of antiretroviral therapy. Results and Conclusions: Brain is one of the viral sanctuary sites for HIV. The current need of neuro-AIDS therapy is to target the brain as a viral reservoir. Drugs should cross or bypass the blood-brain barrier to reach the brain with effective concentrations. Current research on novel drug delivery approaches may prove helpful in treating neuro-AIDS and related disorders effectively.

Background: The Microcrystalline Cellulose is called as a gold standard for the manufacture of pellets. The poor disintegration leads to incomplete drug release that restricts the use of MCC in the immediate-release formulation. Objective: The present work aims to explore non-MCC extruder aid for pellet formulation and solubility modulation potential of Aeroperl® 300 Pharma. Methods: Bicalutamide (BCL) was selected as a model BCS class-II drug. The solubility of BCL was assessed in different vehicles such as polyethylene glycol, propylene glycol, and Tween by carrying out phase solubility study. The suitable vehicle was selected based on the higher solubility of BCL. The vehicle was further adsorbed on newer adsorbent Aeroperl® 300 Pharma to formulate liquisolid granules. The liquisolid granules were further incorporated into the pellet using mannitol and microcrystalline cellulose as an extruder aid. Box-Behnken design was adopted for the optimization of formulation considering MCC: mannitol ratio, the concentration of HPMC and spheronizer speed as independent factors whereas drug release at 30 min, disintegration time and aspect ratio were selected as dependent variables. The pellets were evaluated for different evaluation parameters. Results: Propylene glycol was selected for the formulation of liquisolid technique based on the results of the phase solubility study. Propylene glycol containing BCL was adsorbed on Aeroperl 300 Pharma. The optimized batch was selected exploring the Design-Expert software by considering the limits of different responses. Pellet had excellent flowability. Friability was found to be within the range (<1%). Pellets were found to be spherical and had pores on the surfaces. Conclusion: Liquisolid granules containing newer solubilizer Aeroperl was found to be a promising approach for the improvement in the solubility of the drug. The use of mannitol with MCC has a profound effect on disintegration time, without altering flow property and other parameters. No patents were reported on the combination of Bicalutamide, mannitol and Aeroperl. The critical finding of the present work is to use mannitol as an extruder aid to fasten the disintegration leads to complete drug release within a short period of time. Aeroperl and Mannitol, MCC: mannitol ratio, the concentration of HPMC and spheronizer speed were found to be significant and had the potential effect in pellet formulation.

Objective: Carbonyl stress, resulting from toxic effects of alpha-dicarbonyls such as glyoxal (GO), plays an important role in mitochondrial dysfunction and subsequent development of diabetic complications. This study evaluated the ability of metformin (MET), berberine (BBR), and their combination to prevent GO-induced carbonyl stress in isolated rat liver mitochondria. Methods: Mitochondria (0.5 mg protein/mL) were isolated from the Wistar rat liver and incubated with various concentrations of GO (1, 2.5, 5, 7.5, and 10 mM) for 30 minutes and IC50 for GO was calculated. The suspensions of mitochondria were incubated with various concentrations of MET (2.5, 5, 10, and 20 mM) or BBR (2.5, 5, 10, and 20 μM) for 30 min and then GO in a dose of IC50 at 37 ºC for 30 min. Mitochondrial complex II activity, mitochondrial membrane potential (MMP), MDA level, reactive oxygen species (ROS) formation, reduced glutathione (GSH) content, and protein carbonylation were assessed. The combination index and isobologram of MET and BBR on GO toxicity were calculated. Results: IC50 of GO was assigned approximately 3 mM. GO disrupted the electron transfer chain and significantly increased mitochondrial ROS formation, protein carbonylation, and MDA level. GO decreased mitochondrial viability, MMP, and GSH content. Pre-treatment with MET and BBR could potentially reverse GO-induced deleterious effects in a concentration-dependent manner. Results of the drug combination indicated that CI for Fa 0.5 (Effect 50 %) was 0.83. Conclusion: These results suggest that BBR in combination with MET has a moderate synergistic effect on GO-induced carbonyl stress in isolated rat liver mitochondria.

Background: Venlafaxine HCl is a selective serotonin reuptake inhibitor, which is given in the treatment of depression. The delivery of the drug at a controlled rate can be of great importance for a prolonged effect. Objective: The objective was to prepare and optimize the controlled release core in a cup matrix tablet of venlafaxine HCl using the combination of hydrophilic and hydrophobic polymers to prolong the effect with rate controlled drug release. Methods: The controlled release core in cup matrix tablets of venlafaxine HCl was prepared using HPMC K5, K4, K15, HCO, IPA, aerosol, magnesium stearate, hydrogenated castor oil and micro crystalline cellulose PVOK-900 using wet granulation technique. Total ten formulations with varying concentrations of polymers were prepared and evaluated for different physicochemical parameters such FTIR analysis for drug identification. In-vitro drug dissolution study was performed to evaluate the amount of drug release in 24 hrs, drug release kinetics study was performed to fit the data in zero order, first order, Hixson-crowell and Higuchi equation to determine the mechanism of drug release and stability studies for 3 months as observed. Results: The results of hardness, thickness, weight variation, friability and drug content study were in an acceptable range for all formulations. Based on the in vitro dissolution profile, formulation F-9was considered to be the optimized, extending the release of 98.32% of drug up to 24 hrs. The data fitting study showed that the optimized formulation followed the zero order release rate kinetics and when compared with the innovator product (flavix XR), showed better drug release profile. Conclusion: The core-in-cup technology has the potential to control the release rate of freely water soluble drugs for single administration per day by optimization with the combined use of hydrophilic and hydrophobic polymers.

Background: Metoclopramide hydrochloride (MCP), a derivative of para-aminobenzoic acid, which is a freely soluble drug, gets rapidly absorbed from the gastrointestinal tract and is used in the management of gastrointestinal disorders such as gastric stasis, gastroesophageal reflux and for the prevention of cancer chemotherapy induced emesis. Several brands of MCP are available in Saudi Arabia. Objective: The objective of the present study was to evaluate the quality of different marketed products of MCP tablets 10mg, which were purchased from the retail pharmacy outlets in Abha, Riyadh and Jeddah, Saudi Arabia with a view to determine their interchangeability in clinical practice. Methods: The study was carried out on branded tablets by quality control tests such as weight variation, hardness, friability, disintegration and dissolution. The results of all marketed products complied with the official specifications. Results: The results showed that all the parameters for MCP tablets were in accordance with the USP limits. All the tested four brands were bioequivalent and complying with the official tests for weight variation, friability, disintegration and dissolution tests. The percent friability was also within the specified limit. Moreover, all formulations disintegrated within 2-6 min. The percentage content of the active ingredient of four brands of MCP tablets showed values within the monograph specifications (95-105%). Conclusion: All the four brands evaluated in the present work could be considered bio pharmaceutically equivalent and therefore, patients can safely switch from one brand to another when there is the unavailability of a particular brand.

Background: Rational drug use comprises aspects of prescribing, dispensing, and patient use of medicines for different health problems. This study is aimed to assess drug prescribing practices based on the world health organization prescribing indicators in Mizan-Tepi University teaching hospital. Methods: An institutional-based, retrospective, cross-sectional study was conducted to evaluate the prescribing practices in Mizan-Tepi University teaching hospital. Data were collected based on the World health organization's drug use indicators using prescription papers. A total of 600 prescriptions, written for a 1-year time, dispensed through the general outpatient pharmacy of the hospital were collected by a systematic random sampling method from Mizan-Tepi University teaching hospital. Results: The present study found that the average number of drugs per prescription was 2.04 ± 0.87 in Mizan-Tepi University teaching hospital, with a range between 1 and 5. Prescribing by generic name was 97.6%, and 47.8% of prescriptions contained antibiotics in the hospital. 27.7% of prescriptions contained at least one injectable medication in Mizan-Tepi University teaching hospital. From prescribed drugs, 96.7% of them were prescribed from the Ethiopian essential drug list. Conclusion: Present study indicated that the average number of drugs prescribed per encounter, the percentage of generic prescribing, and prescribing from the EDL were close to the optimal value. However, the percentage of encounters with antibiotics and injections prescribed was found to be very high. Thus, the study highlights some improvements in prescribing habits, particularly by focusing on the inappropriate consumption of antibiotics and injections.

Objective: The present research work focuses on experimental design assisted In-situ gel for fixed dose combination. Significance: Brinzolamide(BZ) BCS class II drug and Timolol Maleate (TM), a BCS class I drug is formulated for obtaining the sustained effect, increased ocular bioavailability and reduction of dose leading to better patient compliance. Methods: The material attributes were gelrite, hydroxy propyl methyl cellulose K4M(HPMC K4M) and HP-β-CD and critical quality attributes identified were gel strength, mucoadhesive index and percentage of drug release of both drugs. BZ and TM were successfully formulated in ion-triggered In-situ gelling system using Taguchi design with minimum trials. Results: The final optimized formula 0.5 %w/v gelrite, 0.5 %w/v HPMC K4M, 1:2.5 Ratio of drug to HP-β-CD as well as 150rpm stirring rate exhibited acceptable results with enhanced solubility of BZ. The pharmacodynamic study revealed a decrease in intraocular pressure for In-situ gel (17.3) compared to conventional marketed suspension. Moreover, delayed mean residence time and high AUC (61.237 and 4523.65) of In-situ gel indicates prolonged residence time with sustained release. Conclusion: In conclusion, excellent ocular tolerance and longer action of gelrite and HPMC K4M. In-situ gel for BZ and TM can be explored as potential alternative to marketed formulation reducing the frequency of administration and improving patient compliance in glaucoma.

Introduction: Modified Epley’s maneuver is the recommended treatment for the Posterior Canal (PC) BPPV. To enhance the efficacy of this maneuver, an easy to perform visual aid device (DizzyFIX) guided modified Epley’s maneuver was studied. Material and Methods: This prospective, double-blind, randomized study included consecutive patients with PC-BPPV based on clinical history, neuro-otological examination, and positive Dix- Hallpike (DHP) test from January 2018 to March 2019 at a neurology clinic of western India. Patients were randomly assigned treatment with either visual aid device assisted modified Epley’s maneuver, which constituted the case group or by a placebo device guided modified Epley’s maneuver, which constituted the control group. DizzyFIX was used as a visual aid device in the case group. Patients were followed up at one hour and 24 hours with DHP by the blinded examiners to observe for remission. Results: Out of 280 patients (140 patients in each group), 6 from the case, and 2 from the controls were lost from the follow-up. Overall, 134 cases were compared to 138 controls. The success rate of remission in the case and the control group at one-hour was 79.19% vs. 48.30%, respectively, with a p-value of 0.003. Similarly, the success rate in the case and control group at 24 hours was 95.27% vs. 80.62%, respectively, with a p-value of 0.011. At 1 hour, unadjusted Odd Ratio (OR) was 4.13, (C.I. 95% 2.02- 8.46) and at 24 hours, it was 4.37, (C.I. 95% 1.39-13.77), which was significant even after adjustment of co-variables (OR 4.02, C.I. 95% 2.34- 8.26) and (OR 4.11, C.I. 95% 2.30- 14.26), respectively. Conclusion: For short term treatment of PC-BPPV, DizzyFIX assisted modified Epley’s maneuver is more efficacious than unassisted modified Epley’s maneuver.

Background: Olmesartan medoxomil is an angiotensin II receptor blocker antihypertensive drug, which has low oral bioavailability because of poor aqueous solubility. Objective: The objective of the present research is the development and optimization of Olmesartan medoxomil loaded self-micro emulsifying drug delivery system by D-optimal mixture design to improve its dissolution rate. Methods: Solubility of Olmesartan medoxomil was determined in different oils, surfactants and cosurfactants. The pseudo ternary diagram was constructed for the identification of self-micro emulsification region. The D-optimal mixture design was employed for the optimization of SMEDDS formulations wherein the factors optimized were the concentration of oil (X1), surfactant (X2), and co-surfactant (X3) and the response was globule size (Y1) and dissolution rate (Y2). Developed selfmicroemulsifying drug delivery system was further assessed for self-emulsification time, drug loading capacity, transparency, globule size, in vitro dissolution and comparative in vitro dissolution testing of optimized formulation with pure medicament and commercially available product. Results: The application of D-optimal mixture design resulted in 14 batches out of which F-5 was found to be the optimized batch which contained Olmesartan medoxomil (20 mg), Capmul MCM EP (23% v/v), Kolliphore EL (49% v/v) and Transcutol P (28% v/v) having globule size of 105 nm, 94.7% dissolution within 30 minutes. In vitro dissolution rate of the drug from SMEDDS was appreciably higher than that of pure drug and marketed products. Conclusion: Olmesartan medoxomil self-microemulsifying drug delivery system was successfully developed and this approach could prove to be suitable for the improvement of the dissolution rate of BCS II class drugs.