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Background: Vildagliptin 50 mg once-daily is a clinically established anti-diabetic therapy in combination with a sulphonylurea and renally impaired patients. We developed sustained release (SR) vildagliptin 50 mg tablet formulation for prolongation of dipeptidyl peptidase-4 (DPP-4) inhibition coverage. The present study compares the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of investigational vildagliptin SR 50 mg tablet with Galvus® in healthy Indian adult males after single and multiple-dose administration.Methods: Each randomized, open-label, two-period, cross-over study enrolled 36 healthy Indian adult male subjects for the assessment of single and multiple-dose PK/PD profiles of SR 50 mg vildagliptin under fed condition. The plasma drug concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. PK parameters (Cmax (ng/ml), AUC0-18, AUC0-36, and AUC0-τ (ng.hr/ml), Tmax (hour), t1/2 (hour), Tmaxss (hour), Cτss (ng.hr/ml) were calculated using Phoenix® WinNonlin® software. The DPP-4 inhibition was determined in a fluorescence-based assay.Results: Vildagliptin SR tablet showed prolonged PK/PD characters compared to Galvus®. All PK parameters expressed as Mean±SD. The single-dose PK measures were Cmax (58.22±11.31), AUC0-18 (556.92±135.84), AUC0-36 (608.82±159.84), Tmax (6.48±3.78). In the multiple-dose study, PK findings were Cmax (73.20±17.71), AUC0-τ (714.36±303.21), Cτss (4.15±6.51), Tmaxss (5.60±3.12). Vildagliptin SR 50 mg achieved prolonged DPP-4 inhibition (≥80%) for18-20 hours after single and multiple-dose administration as compared to Galvus® (12-13 hours).Conclusions: Investigational vildagliptin SR tablet was found safe, well-tolerated after single and multiple-dose administration. Its extended DPP-4 inhibition profile compared to Galvus® may benefit the patient population on combination therapy with a sulphonylurea and renally impaired patients.

Recently, focus on the development of controlled release drug delivery system has increased, as existing drugs exhibit certain pharmacokinetic limitations. The major goal of designing sustained release formulations is to improve the drug performance by prolonged duration of drug action, decreased frequency of dosing and reduced side effects by using smallest quantity of drug administered by the most suitable route. Osmotic-controlled release oral delivery system (OSMO technology) is the most promising strategy based system for sustained delivery of drug. Drug can be delivered in a controlled manner over a long period of time by the process of osmosis. Osmotic drug delivery system appears to be a promising solution for the limitations of conventional extended release formulations by virtue of their distinguished technological features. The present review describes briefly about various controlled drug delivery systems with special focus on advantages of osmotic-controlled release oral delivery system related to diabetes therapy and improved compliance.

Tendinopathy is a common disease that is difficult to manage due to its recurrent nature. It is associated with increased healthcare costs and significantly impacts quality of life of patients. Also, according to recent studies patients with high cholesterol and diabetes are at a higher risk of developing tendinopathy. There has been rise in the incidence of tendinopathies due to increase in sport activities, life expectancy and some other factors (environment, diet and some drug therapies). Approximately 30% of visits for musculoskeletal pain in general practice are related to tendon injury. Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids remain the mainstay of treatment. Despite the use of current therapies, there is need of a supportive therapy that can help in the healing process towards development of physiologically normal tendons. Nutraceuticals have been used as supportive therapy for management of tendinopathies. This review focuses on the management of tendinopathy with special attention on role of nutraceuticals such as type I collagen, mucopolysaccharides and vitamin C in the management of tendinopathy. Clinical data suggests that this combination (type I collagen, mucopolysaccharides and vitamin C) promotes the endogenous synthesis of collagen type I, avoiding the accumulation of collagen type III and aggrecan, thus interfering with the degeneration of tendon tissue. Based on the available clinical data, combination of type I collagen, mucopolysaccharides and vitamin C not only reduce the clinical symptoms but also improve structural evolution of different types of tendinopathies as well as plantar fascitis.

Staphylococcus aureus (S. aureus) is a Gram-positive facultative anaerobic bacterium that colonizes the skin and nasal passages of humans. The incidence of invasive S. aureus infections has increased over the past decades and is associated with poor outcomes and high mortality rates. S. aureus is responsible for almost one-third of acute bacterial skin and skin structure infections with methicillin-resistant Staphylococcus aureus (MRSA) accounting for a large proportion of these. The S. aureus strains prevalent inIndia are more aggressive and there are recent reports of the emergence of the more virulent multidrug resistant lineages ST2371 and ST8. Management of these infections is complicated by the fact that antimicrobial stewardship is non-existent, the choice of treatment is often empirical and available treatment options are limited due to a high prevalence of resistance strains. Currently available anti-MRSA agents include vancomycin, teicoplanin, linezolid, daptomycin, tigecycline, and clindamycin. However, the emergence of resistant strains and several undesirable features related to the safety and tolerability of these agents have limited the options available for the management of MRSA infections. A newer, safe and efficacious antibiotic is thus an unmet need for the management of MRSA in patients with acute bacterial skin and skin structure infections. In this review we explore the current and future trends in the management of acute bacterial skin and skin structure infections highlighting the challenges in their management in India, and current progress in the development of some novel drugs for the management of MRSA infections.

Background: Although nadifloxacin has been shown to be effective in the treatment of skin & soft tissue infections (SSTI), there is a paucity of data comparing its efficacy and safety with other antibacterials, especially in Indian paediatric population. Therefore, objective of this study was to compare the safety and efficacy of nadifloxacin with mupirocin in children with SSTI.Methods: This was a single-centre, open label, randomized, parallel group, comparative study in 60 children of

Background: Recurrent respiratory infections (RRIs) are common in children especially in age 1 to 6 years. Pidotimod, an immunostimulant has been found to lower the recurrences of RRIs and improve the quality of life. The Objective of this study was to assess the efficacy and safety of pidotimod in children with recurrent respiratory infections (RRIs).Methods: In this single-centre, prospective, observational study, children aged 2 to 15 years diagnosed with RRIs were included. RRIs were defined as occurrence of 3 or more episodes of acute respiratory infections (ARIs) or more than 15 days of respiratory symptoms in the past 3 months. These children were treated with pidotimod in addition to standard care treatment. Treatment duration was two months and the follow-up continued for three months. Number of RRIs and severity of RRIs, antibiotic courses and rate of hospitalization before and after treatment were compared.Results: In total 25 children included in the study, mean age was 7.34±3.63 years. Among them, 68% were males. After treatment with pidotimod, there was significant reduction in mean number of ARI episodes (3.84±0.85 at baseline to 0.48±0.51 at follow-up, p

Background: In India, gram-positive infections (GPIs) particularly, methicillin-resistant Staphylococcus aureus (MRSA) prevalence is reported to increase exponentially. The overall mortality rate among patients with multi drug resistant GPIs in ICU setting are as high as 16%, despite the availability of various therapeutic options. Aim of the study is to determine the burden of GPIs in critical care settings and to understand the practising behaviour among the specialists in the management of MRSA infections.Methods: The survey was conducted among 264 critical care specialists who attended the Annual National Conference of Indian Society of Critical Medicine held in February 2019 at Mumbai. The delegates were administered a validated 10 question survey.Results: In the survey, 72% of the respondents agreed to the rising prevalence of MRSA and associated increased mortality rate of >16%. Empirical gram positive cover is being given to 30-40% of ICU patients, with ABSSSI being listed as a major indication followed by CAP, VAP, CLABSI and DFI. 46% of the doctors listed vancomycin as their preferred anti-MRSA agents followed by teicolplanin and linezolid. However, more than 80% of the doctors feel that nephrotoxicity in vancomycin, thrombocytopenia in linezolid and poor biofilm penetration are major limitations of these anti-MRSA agents.Conclusions: The survey highlighted the increasing trend in the prevalence and associated mortality in GPIs in critical care settings in India. Further, the limitations of existing anti-MRSA agents have invoked the need for a newer agent with a broad spectrum anti-bacterial activity along with improved safety profile and effective biofilm penetration, which can be used as a suitable alternative empiric therapy to manage GPIs.

Osteoarthritis (OA) is a common musculoskeletal disorder that affects large and small joints and is seen in all ages due to diverse aetiologies. Pain, joint stiffness and limitation of daily activities affects the quality of life of individuals with OA. Conventional analgesics like non-steroidal anti-inflammatory drugs affect pain and inflammatory component but do not target the disease pathogenesis. Damage to the joint cartilage is central to the pathogenesis of OA. Better understanding of the pathogenesis has led to evolution of various adjuvant drugs in management of OA. Among them, undenatured type II collagen induces immune tolerance and thereby provide benefits by reducing the joint damage. Studies assessing efficacy and safety of undenatured type II collagen in OA have shown to reduce clinical symptoms like pain, joint stiffness and improvement in physical activities, and thus improving the quality of life. It is well tolerated and safe for use in OA. This article discusses the pathophysiology of OA with inflammation and beyond, and overviews the various drugs that are used as adjuvants in the management of OA with special focus on the use of type 2 collagen.

Background: Numerous dietary supplements with disease-modifying action are available in Indian market. However, doctor’s preferences for these disease modifying osteoarthritis drugs (DMOADs) to prevent progression of OA are not known. The objective of this study was to quantify doctor preferences for potential DMOADs.Methods: The survey instrument (online survey questionnaire at survey monkey) was developed by researchers upon review of existing literature and detailed discussion with practicing clinicians. Face and content validity and reliability (test-retest method) was assessed through a focused panel of clinicians to determine if content was adequate to obtain the necessary data. This was a cross-sectional digital survey of 207 orthopaedicians during Indian Orthopaedic Association Conference-2018 organized at Coimbatore.Results: NSAIDs + DMOAD combinations were the most preferred treatment option for newly diagnosed OA patients. 44% orthopaedicians prefer to start the treatment with combination of NSAID and DMOAD as compared to 10% with paracetamol monotherapy. Glucosamine/chondroitin combinations are the most commonly preferred DMOAD by the orthopaedicians; followed by undenatured type II collagen. 66% of the doctors surveyed opined that the efficacy of undenatured type-II collagen is better as compared to other DMOADs.Conclusions:The findings from the survey suggest that majority of orthopaedicians prefer to prescribe NSAID with DMOAD combinations for newly diagnosed osteoarthritis patients.

Most of the insulin formulations in clinical use contain phenol, meta-cresol or both as excipients. These excipients in insulin preparations provide stability and have antimicrobial properties. However, they are reported to be associated with undesirable side-effects especially localised allergic reactions. Amount of excipients injected per unit dose of insulin is a major determining factor in causation of these reactions. This review discusses the excipients in different insulin formulations available in India with potential of precipitating undesirable effects and the use of concentrated insulins to reduce these complications. To avoid the detrimental effects associated with excipients, removal of preservatives or use of insulin preparations devoid of excipients can be an option. Besides these approaches, one approach that can be considered is the use of concentrated insulin to reduce the volume of insulin dose and thereby the excipients. Concentrated insulins address the high insulin requirements of the growing population of patients with type 2 diabetes who require higher insulin doses. Concentrated insulins help in reduction of dose volume as well as amount of excipients injected per unit dose of insulin. U200 (concentrated r-DNA Human Insulin Premix 30/70-200 IU/ml) can be advantageous with better absorption from smaller quantity injected, lesser variability in absorption, lesser pain and discomfort due to smaller quantity, lesser chances of hypoglycaemia all of which can lead to better patient compliance. Thus, concentrated insulin U200 can be one of the alternatives to prevent/reduce clinical complications with excipients in insulins.

Background: Osteoarthritis (OA) is the most common musculoskeletal conditions affecting the quality of life. Undenatured collagen type II has emerged as one of the promising treatment options in treatment of OA. Despite being available in India, clinical safety and efficacy have not been evaluated. We performed a non-interventional, real-life study to determine its safety and efficacy in Indian population.Methods: A non-interventional, real-life study was performed in patients with OA of knee by 18 orthopaedicians in India. Patients enrolled were followed-up at day 30 (visit 2), day 60 (visit 3) and day 90 (visit 4). Efficacy was assessed by Western Ontario McMaster Osteoarthritis Index (WOMAC) and Visual Analogue scale (VAS) on each visit. Safety was assessed by incidence of suspected adverse events (AEs), and abnormal laboratory parameters.Results: Among 291 enrolled patients 226 patients completed the study. Mean age of the population was 56.2±8.7 years and 53.3% of them were females. In 291 patients included in safety analysis, at least one treatment emergent adverse event (TEAE) was seen in 4.47% patients. None of the AEs were serious or resulted in termination of patient from the study. Nausea (1.37%) and headache (1.03%) were the common AEs. Treatment with undenatured collagen type II was associated with significant reduction in WOMC score (pConclusions: Undenatured collagen type II is safe and efficacious in Indian patients with OA. This can be considered early in the initial management of OA.

Background: Recently, management of type 2 diabetes mellitus (T2DM) has changed with advent of novel agents like DPP4i, SGLT2i and GLP-1 agonist. Of these, DPP4i have emerged as promising agents as monotherapy and as an add-on to metformin for improved glycaemic control. This survey was planned to explore current prescribing trends of physicians of India for the management of T2DM.Methods: This was a prospective, cross sectional, questionnaire-based survey of physicians and endocrinologist across different geographic areas in India. A survey questionnaire consisting of 10 questions related to management of T2DM in real-world clinical settings was prepared, validated in a small group of physicians and then administered to physicians and endocrinologists.Results: Responses from 502 physicians were received. About 60% physicians prefer DPP4i as first add-on to metformin followed by sulfonylurea (SU) (30%). Amongst DPP4i, vildagliptin and sitagliptin were preferred by 48% and 28% physicians respectively as first add-on to metformin. For patients uncontrolled on metformin + SU therapy, 54 % physicians prefer DPP4i as second add-on. Vildagliptin is perceived to have the better efficacy and safety data, as suggested by 40% and 43% physicians respectively. Large number of physicians (48%) were hesitant to prescribe teneligliptin due to insufficient data. SGLT2 inhibitors are preferred as third add-on by 44% physicians.Conclusions: DPP4i are being increasingly preferred by physician as an add-on to metformin. Among DPP4i, the survey revealed that vildagliptin is the most preferred DPP4i as an add-on to metformin possibly owing to its established safety and efficacy data.

Hypertension is attributed to be one of the major risk factors in the pathophysiology of ischemic heart disease, stroke, heart failure and renal dysfunction. Angiotensin receptor blockers (ARBs) are one of the first line drugs recommended for clinical use in hypertension by JNC 8. Azilsartan is the recent addition to this family of ARBs and is perceived as one of the potent antihypertensive drugs today. Azilsartan was developed by replacing the tetrazole ring in candesartan with a 5 member oxo-oxadiazole ring. In India Azisartan was recently approved by DCGI in December 2016 for use in hypertension. In various randomized, double blind clinical studies Azilsartan was found to be to be superior in terms of clinical efficacy over other ARBs like Candesartan, Olmesartan and Valsartan and angiotensin converting enzyme inhibitor like Ramipril. In terms of safety profile Azilsartan appears to be equivalent to the currently available ARBs. Azilsartan due to its superior efficacy and comparative safety profile appear to be a new addition to the armamentarium in the treatment of hypertension.

Diabetic Nephropathy has become the single most import cause of End Stage Renal Disease (ESRD). Various strategies to limit or slow the progress the Diabetic nephropathy are suggested by the guidelines and evidences. By maintaining strict glycemic control the progression of diabetic nephropathy can be altered. Glycemic control in diabetic patients with nephropathy is complex as falling eGFR renders many ant diabetic medications contraindicated while others are needed to be done in low dose. The intent of this review article is to collate the available evidences for renal safety with one such anti diabetic class of medication, dipeptidyl peptidase 4 inhibitor and evaluate the guideline based antidiabetic treatment in Type 2 Diabetes Mellitus patients with renal insufficiency.