Formulation and Evaluation of Sitagliptin Phosphate and Metformin Hydrochloride Trilayered tablets

Sitagliptin phosphate when used alone is an oral anti hyperglycemic drug of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. It is available as tablets under trade name JANUVIA. Metformin hydrochloride is used alone in the form of biguanide anti hyperglycemic agent for treating non-insulin-dependent diabetes mellitus (NIDDM) and is available as both conventional and sustained release tablets. The objective of the present study was to develop a trilayered tablet of immediate release Sitagliptin phosphate layer and sustained release Metformin Hydrochloride layer. Apart from the aesthetic appeal this trilayered tablet is expected to improve glucose tolerance in patients with the type 2 diabetes by lowering both basal and postprandial plasma glucose, reducing the dose, reducing frequency of administration and dose related gastrointestinal side effects of metformin and improve its bioavailability thus improving the patient compliance. Metformin Hydrochloride has biological half-life of nearly 6 hours. An attempt was made to sustain its release by using two different polymers in two layers. Preformulation studies including drug excipient compatibility studies were conducted for both drugs. Different formulations of sustained release Metformin HCl tablets were prepared by using a combination of hydrophilic polymers like HPMC K100, HPMC K4M, HPMC K15 M, pH sensitive polymer Carbopol 971P, retarding polymer Ethyl cellulose and Low substituted hydroxy propyl cellulose. Sitagliptin immediate release formulations were prepared using cross povidone, croscarmellose sodium and sodium starch glycolate as super disintegrants. The tablets were evaluated for all physico chemical parameters like angle of repose, bulk density, tapped density, Hausners ratio and carr’s index. Based on the invitro dissolution data the formulations SF6, MF9 and MF8 were found to be the optimized formulations for Sitagliptin phosphate and Metformin Hydrochloride formulations respectively. Trilayered tablets were prepared by first preparing Metformin HCl layers namely MF3 and MF8 using lesser compression force. The final compression was made by placing Sitagliptin IR layer (SF6) on the Metformin layers with final hardness of 6.5 kg and evaluated. The IR layer of Sitagliptin phosphate layer disintegrated in 54.67 sec from the trilayered tablet. In vitro dissolution studies of Trilayered tablet were performed in USP type II apparatus. The cumulative % drug release of Sitagliptin phosphate SF6 was found to be 99.65% at 30 min and Metformin HCl MF3 and MF8 was found to be 98.72 % at 12 hrs. From the study it is found that the formulations made from MF3 and MF8 combination of HPMC K15M and HPMC K4M polymers and SF6 Sodium starch glycolate used as super disintegrant was found to show optimum properties of required drug release

FORMULATION AND EVALUATION OF PARENTERAL METHOTREXATE NANOLIPOSOMES

Objective: The objective of the present study was to encapsulate Methotrexate in liposomal formulation for treatment of cancer. Conventional compositions of Methotrexate are available but in high doses showvariation in bioavailability and they are associated with a number of toxicities when administered orally. To overcome these problems, in the present study, inclusion of Methotrexate in parenteral liposomal formulation was approached with the aim of increasing retention time at the site of action which leads to improvement in bioavailabilityand better tumor targeting. Methods: In this study, PEGylated Methotrexate liposomes containing Hydrogenated Soy Phosphatidyl Choline and Cholesterol were prepared by thin film hydration method. The main advantage of PEGylated lipid vesicles lies in the possibility of active-targeted delivery of drugs to the tissues or organs that need those most. Attempts were made to enhance the encapsulation by use of non-ionic surfactants such as Tween-80, Tween-20 and solubilityenhancers such as β-cyclodextrin. The characterization of formulated liposomes was carried out by vesicle size, zeta potential, %free drug and in-vitro dissolution. Results: Formulation containing 10mg/ml of Tween-20 and 20 mg/ml of β-cyclodextrin showed highest encapsulation efficiency. The optimized formulation has exhibited more than 90% release of the drug within a period of 4 days. The accelerated stability studies (40±2°C/ 75±5% RH) of the Methotrexate liposome were conducted for a period of three months and the formulation was found to be stable. Conclusion: These results suggest that the liposome encapsulated MTX may serve as a useful targeted drug delivery system for effective management of neoplastic diseases

FORMULATION AND EVALUATION OF BILAYERED TABLETS OF MONTELUKAST AND LEVOCETRIZINE DIHYDROCHLORIDE USING NATURAL AND SYNTHETIC POLYMERS

The objective of present work was to formulate and evaluate bilayered tablets of Levocetrzine and Montelukast for treating allergic rhinitis effectively. Anti-allergic medicines (eg, some antihistamines) can cause adverse events such as somnolence and sedation. The Combining Montelukast with Levocetirizine gives additional benefits in comparison with either drug alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis. Montelukast sodium is alkaline stable (bioavailability 64%), most of drug being absorbed from the intestine while Levocetirizine Dihydrochloride is acid stable. When tablets of the combination of these are  prepared, they tend to become unstable during the shelf life of the formulation. Hence it is recommended to prepare a bilayer tablet, by formulating Montelukast in sustained release layer and Levocetrizine as immediate release layer as it improves and increases the stability by reducing the acid base interactions of both the drugs in combination there by increasing the bioavailability. Taking this into account different formulations were prepared by wet granulation method using natural Tamarind Seed Polysaccharide and synthetic HPMCK100,K15M and K4M release rate controlling hydrophilic polymers. The formulations were evaluated for hardness, weight variation, friability, swelling index and drug content uniformity. The in vitro release of drug from the formulations was studied in pH 1.2 acidic buffer and pH 7.4 phosphate buffer, and it was found that the prepared tablets were able to sustain the release of the drug upto 12hours. The release of Montelukast and Levocetrizine of both layers from the tablets was found to be diffusion controlled and the release mechanism was non-Fickian based on the n value of Korsmeyer-peppas plot. The FTIR studies were performed on three optimized formulations (F4, F12, F16) and the plain drug controls(Levocetrizine,Montelukast).From the  observed peaks it is evident that the polymers used and the drugs were  found to be mutually compatible chemically. The Pharmacokinetic Studies were performed in two groups of male wistar rats. One group was administered with the optimized formulation containing tamarind Seed Polysaccharide(F12) while Plain Montelukast oral suspension acted as control in the second group.The results indicate that the formulation optimised with 1:4(drug:TSP) was able to sustain the release of montelukast upto 12hours.Insrease in Tmax and AUC(0-α) also were also observed in the studies indicating efficient sustained action and improved bioavailability of the drug. The formulated bilayered tablets using natural polymers provided immediate release of Levocetrizine and sustained release of Montelukast and therefore hold promise as an alternative dosage form in the treatment of allergic rhinitis and bronchial asthma. Key words: Tamarind Seed Polysacharide, Hydroxypropyl methyl cellulose,  Bilayered tablets

STUDY OF ANTI-ANAEMIC EFFECT OF SCHREBERA SWIETENIOIDES ROXB. IN RAT MODELS

Objective: Ethnobotanical survey of Schrebera swietenioides Roxb revealed the bark of the tree to be useful in anemia. The objective of this study wasto study the ant-anemic effect of methanolic extract of root bark of S. swietenioides Roxb. against phenylhydrazine induced anemic rat model.Methods: The methanolic extracts of Leaf, Stem bark, and Root bark were prepared by soxhlation. Phytochemical analysis of the extracts was performedusing standard testing procedures. The total phenolic content (TPC) of Schrebera leaf extract, Schrebera stem bark extract and Schrebera root barkextract (SRE) was determined by Folin–Ciocalteu method. Hemolytic anemia was induced in male Wistar rats by intraperitoneal administrationof phenylhydrazine HCl (PHZ) at doses of 40 mg/kg body weight/day for 3 consecutive days. Anemic rats were orally treated with SRE at doses of200 and 350 mg/kg body wt/day. The rats were analyzed for hematological parameters such as hemoglobin (Hb), red blood cell count (RBC) andhematocrit or packed cell volume (PCV) on day 4 and 14.Results: Phytochemical screening of the extracts indicated the presence of carbohydrates, saponins, sterols, polyphenols, tannins, and flavonoids.Folin–Ciocalteu method of testing for TPC demonstrated SRE to be rich in total phenols with a value of 266 mg GAE/g of dry extract. Anemia wasinduced successfully in Groups II, III, IV, and V, which was indicated by a mean reduction of 51.6% in RBC count; 53.85% in Hb content, and 54.9% inPCV. Analysis of hematological parameters on day 14 showed that SRE significantly (p<0.05) improved Hb, RBC count, and PCV at a dose of 350 mg/kgbody weight.Conclusion: This study, not only substantiates the folklore use of the root bark of S. swietenioides, but also suggests its inclusion in the treatment ofanemia as it exhibited significant anti-anemic activity.Keywords: Schrebera swietenioides, Anemia, Hematological parameters, Phenyl hydrazine, Hematocrit

ENHANCED TRANSDERMAL PERMEABILITY OF TELMISARTAN BY A NOVEL NANOEMULSION GEL

Objective: Telmisartan is an angiotensin II type I receptor blocker antihypertensive agent with 42% oral bioavailability. The aim of the present investigation was to develop a nanoemulsion gel to enhance bioavailability of poorly water soluble Telmisartan.Methods: Different nanoemulsion components (oil, surfactant and co-surfactant) were selected on the basis of solubility and emulsification ability. Pseudotemary phase diagrams were constructed using aqueous titration method. Carbopol 934 was added as a gel matrix to convert nanoemulsion into nanoemulsion gel. Drug loaded nanoemulsions and nanoemulsion gels were characterized for particle size, viscosity, rheological behavior, thermodynamic stability studies and ex vivo permeation studies using rat skin. Transdermal permeation of Telmisartan from nanoemulsion gels was determined using Franz Diffusion cell.Results: The optimized nanoemulsion gel (NEG) contained Labrafil®M 2125 CS (14.3%) as oil, Acrysol®EL 135 (30.84%) as surfactant, Carbitol® (15.42%) as co-surfactant and (32.44%) water; 20 mg drug and 1% w/w carbopol. The ex vivo permeation profile of optimized formulation was compared to nanoemulsion and normal gel. Permeability parameters like steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) were significantly increased in nanoemulsion (NE) and nanoemulsion gel (NEG) as compared to conventional gel. There was a considerable improvement in bio availability for nanoemulsion gel compared to the conventional telemisartan gel.Conclusion: Nanoemulsion gel has significantly increased the bio-availability of the drug.Â

PREPARATION, PHYSICAL CHARACTERIZATION, AND PHARMACOKINETIC STUDY OF DOCETAXEL NANOCRYSTALS

Objective: The main objective of this study was to prepare and evaluate the nanocrystal formulation of docetaxel. Methods: Docetaxel nanocrystals were formulated to improve the water solubility. Docetaxel nanocrystals were prepared by nanoprecipitation method using Tween 80, egg lecithin, and povidone C-12 as stabilizers and poly(lactic-co-glycolic acid) (PLGA) as polymer in acceptable limits. A total of 16 formulations were prepared by changing stabilizer and polymer ratios. The prepared nanocrystals were characterized by particle size, zeta potential, crystalline structure, surface morphology, assay, saturation solubility, and in vitro drug release. Results: Based on particle size, polydispersity index, and zeta potential data, four formulations were optimized. The formulation containing Tween 80 as stabilizer has shown lowest particle size and better drug release than the formulations containing egg lecithin and povidone C-12 as stabilizers. The formulation containing Tween 80 and PLGA has shown still lower sized particles than the Tween 80 alone and exhibited prolonged sustained drug release. The release kinetics of formulations containing Tween 80 and PLGA followed zero-order release kinetics and formulations containing egg lecithin and povidone C-12 followed Higuchi diffusion (non-Fickian). Conclusion: From the study, we concluded that as the type and concentration of stabilizer changed the size and shape of the crystals were also changed and the formulations showed sustained drug release with non-Fickian diffusion

FORMULATION AND EVALUATION OF MONTELUKAST SODIUM AND LEVOCETIRIZINE DIHYDROCHLORIDE SUBLINGUAL TABLETS

 Objective: The objective of the current study was to develop and optimize sublingual tablets of montelukast sodium and levocetirizine dihydrochloridewhich are effective drugs in the treatment of asthma.Methods: The sublingual tablets of montelukast sodium and levocetirizine dihydrochloride were prepared by direct compression method usingsodium starch glycolate, crospovidone (CP), and croscarmellose sodium (CCS) as superdisintegrants. The tablets were evaluated for physicalproperties including hardness, weight variation, thickness, friability, drug content, wetting time, water absorption ratio, in vitro disintegration time,and in vitro dissolution study.Results: The hardness, weight variation, thickness, friability, and drug content of tablets were within pharmacopoeial limits. An optimized tabletformulation F8 was found to have short wetting time of 18.36 seconds, water absorption ratio of 94.42 and in-vitro disintegration time of 45.42 seconds.The results indicated that the amount of super disintegrants such as CP and CCS significantly affected the dependent variables like wetting time, waterabsorption ratio and in-vitro disintegration time. The in-vitro drug release was found to be higher for formulation F8 with 94.59% for montelukastsodium and 95.48% for levocetirizine dihydrochloride within 60 minutes. The drug release improved by 1.88 times for montelukast sodium and1.82 times for levocetirizine dihydrochloride compared to oral marketed immediate release tablet formulation.Conclusion: From the present study, it can be concluded that sublingual route has potential to improve the bioavailability of the drug by avoiding firstpass metabolism, to provide quicker onset of action and to improve patient compliance in the management of asthma.Keywords: Sublingual tablet, Montelukast Sodium, Levocetirizine Dihydrochloride, In vitro dissolution study

EVALUATION OF ANTI-DIABETIC ACTIVITY OF HYDNOCARPUS LAURIFOLIA IN STREPTOZOTOCIN INDUCED DIABETIC RATS.

Objective: The objective of this study was to evaluate the anti-hyperglycemic activity of different extracts of Hydnocarpus laurifolia seeds in both normal and diabetic rats. Methods: Male Wistar rats weighing about 180-250 g were taken and divided into eleven groups, with six rats in each group. Diabetes was induced by giving streptozotocin (30-50 mg/kg) intraperitoneally. Rats that showed blood glucose levels >250 mg/dl were selected for the study. Metformin (50 mg/kg) was given as a standard oral hypoglycemic agent. Oral glucose tolerance test was performed in all groups of rats. Results: The petroleum ether and ethylacetate extracts of H. laurifolia seeds at different doses was prepared and administered orally. The blood glucose levels were estimated by glucose-oxidase method. Anti-hyperglycemic activity of the test drugs in diabetic rats showed a significant reduction in blood glucose levels (p<0.0001) at 1 hr, 2 hr and 4 hrs respectively when compared to diabetic group. Conclusion: The results suggested that H. laurifolia seed extract may have potent anti-diabetic activity, justifying the use of the drug for the treatment of diabetes mellitus. Keywords: Hydnocarpus laurifolia, Achariaceae, Oral glucose tolerance test, Anti-hyperglycemic activit

Prediction of Tuberculosis Using an Automated Machine Learning Platform for Models Trained on Synthetic Data.

High-quality medical data is critical to the development and implementation of machine learning (ML) algorithms in healthcare; however, security, and privacy concerns continue to limit access. We sought to determine the utility of "synthetic data" in training ML algorithms for the detection of tuberculosis (TB) from inflammatory biomarker profiles. A retrospective dataset (A) comprised of 278 patients was used to generate synthetic datasets (B, C, and D) for training models prior to secondary validation on a generalization dataset. ML models trained and validated on the Dataset A (real) demonstrated an accuracy of 90%, a sensitivity of 89% (95% CI, 83-94%), and a specificity of 100% (95% CI, 81-100%). Models trained using the optimal synthetic dataset B showed an accuracy of 91%, a sensitivity of 93% (95% CI, 87-96%), and a specificity of 77% (95% CI, 50-93%). Synthetic datasets C and D displayed diminished performance measures (respective accuracies of 71% and 54%). This pilot study highlights the promise of synthetic data as an expedited means for ML algorithm development