Compounding and Characterization of a Selfmicroemulsifying System of Ticagrelor Tablets for Enhanced Solubility.

Ticagrelor is used to inhibit acute coronary syndrome, but its poor solubility and low bioavailability limit its in-vivo efficacy. The purpose of this study was to manufacture an optimized ticagrelor-loaded self-microemulsifying drug-delivery system in the form of tablets to enhance the solubility and dissolution of that drug. A preliminary study was conducted to determine the extent of turbidity of oils for this study, and a pseudoternaryphase diagram was used to identify the region of formation of microemulsion with 3 ratios (1:1,1:2, and 1:3). The solubility of ticagrelor was determined with the selected oil and a surfactant-and-cosurfactant mixture. A simplex lattice mixture design was used to compound the microemulsion. The microemulsion was converted to granules by the use of an adsorbent (aerosol) after a precipitation study. After characterization, the resultant granules were compressed into tablets for an in-vitro release study. The optimized formulation was subjected to various characterization procedures to determine the zeta potential, particle size, and surface morphology. The solubility of the drug was found to have increased manyfold in all formulations, and the optimized formulation was found to be 221.37 mg/mL. With respect to the ticagrelor tablets, aerosol up to 30% was needed as an adsorbent in the self-microemulsifying drug-delivery system. The compression of the ticagrelor granules was satisfactory for tablet formation. In all formulations, the release of the active drug was more than 80% within 30 minutes of dissolution time. The optimized icagrelorloaded self-microemulsifying drug-delivery system formulation consisted of medium-chain triglyceride oil (47.88.0%), surfactant (28.25%), and cosurfactant (23.85%), which significantly improved the dissolution of ticagrelor. The results of analysis via scanning electron microscopy revealed that the surface and size of the drug and the zeta potential were also satisfactory and suggested that the optimized ticagrelor-loaded self-microemulsifying drug-delivery system described in this report could be successfully used as an efficient method for achieving enhanced dissolution of ticagrelor.

Systematic approach for the formulation and optimization of atorvastatin loaded solid lipid NANOAPARTICLES using response surface methodology.

Atorvastatin is a lipid lowering agent with poor oral bioavailability (12%) because of poor solubility and extensive first pass hepatic metabolism. In order to overcome these issues, atorvastatin loaded solid lipid nanoparticles (ATOR-SLNs) were prepared by using glyceryl tripalmitate as lipid carrier, poloxamer 407 as surfactant and soya lecithin as emulsifier. The purpose of this work was to optimize the formulation with the application of response surface methodology to improve the physicochemical properties. The central composite rotatable design consisting of three factored factorial design with three levels was used for the optimization of the formulations. The optimized formulation was composed of drug/lipid ratio of 1:3.64, surfactant concentration of 1.5% with 5 min time for sonication. Fourier transforms infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies confirmed the compatibility of drug and lipid in the formulation. The optimized ATOR- SLNs showed almost spherical shape with a mean particle size of 338.5 nm, zeta potential of -24.7mV, DL of 17.7% and EE of 81.06% respectively. The in vitro drug release study showed a burst release at the initial stage followed by the prolongation of drug release from lipid matrix. Stability study revealed that ATOR-SLNs were more stable at 4±2˚C when compared with storage at 25±2˚C/60±5% RH during the six months storage period. These results indicated that the developed ATOR-SLNs is a promising approach for increment of bioavailability by improving the physicochemical properties.

Assessment of erythropoietin for treatment of anemia in chronic kidney failure- ESRD patients.

BACKGROUND AND OBJECTIVE: Currently there is an inadequate data regarding effective management of anemia in chronic kidney disease (CKD) patients who are on dialysis. In CKD patients' anemia mainly develops from decreased renal synthesis of erythropoietin (EPO) and iron deficiency. Our current study focused to effective management of anemia in CKD patients'. STUDY DESIGN: Prospective observational case series study. METHODS: Eligible patients were assigned to three study groups according to initial hemoglobin level i.e. Group I having Hb level below 11g/dL, Group II with Hb level of 11-13g/dL, and Group III with Hb level more than 13g/dL. Intravenous dosing of ESA's calculated according to the range of 150-300IU or equivalent microgram quantity per kilogram body weight was administered to patients in divided doses per week; alone or in combination with iron supplements. RESULTS: Study population (n=163; 100%), of which 124 subjects (76%) patients were treated with erythropoietin and iron supplements; rest of 39 (24%) patients were treated with only erythropoietin. The estimation of hemoglobin content revealed Group I (98 patients) Hb were increased significantly from 9.0±1.2g/dl at baseline to 10.9±1.7g/dl. No significant changes in Group II and Group III were observed. CONCLUSIONS: Study suggests use of erythropoietin along with iron for treatment of renal failure associated anemia is more beneficial for CKD patients having low Hb. Also study conclude the use of lower than normal dose (150-300IU) of ESA is appropriate when hemoglobin reaches 11g/dl in hemodialysis patients.

Prescription patterns and appropriateness of antibiotics in the management of cough/cold and diarrhea in a rural tertiary care teaching hospital.

BACKGROUND: Acute gastroenteritis and respiratory illnesses are the major causes of morbidity and mortality in children under 5 years of age. The objective of this study was to evaluate the prescription pattern of antibiotic utilization during the treatment of cough/cold and/or diarrhea in pediatric patients. METHODS: A descriptive, cross-sectional study was conducted for 6 months in pediatric units of a tertiary care hospital in South India. Children under 5 years of age presenting with illness related to diarrhea and/or cough/cold were included in this study. Data were collected by reviewing patient files and then assessed for its appropriateness against the criteria developed in view of the Medication Appropriateness Index and Guidelines of the Indian Academy of Pediatrics. The results were expressed in frequencies and percentages. Chi-square test was used to analyze the data. A P < 0.05 was considered statistically significant. RESULTS: A total of 303 patients were studied during the study period. The mean age of the patients was 3.5 ± 0.6 years. The majority of children were admitted mainly due to chief complaint of fever (63%) and cough and cold (56.4%). The appropriateness of antibiotic prescriptions was higher in bloody and watery diarrhea (83.3% and 82.6%; P < 0.05). Cephalosporins (46.2%) and penicillins (39.9%) were the most commonly prescribed antibiotics, though the generic prescriptions of these drugs were the lowest (13.5% and 10%, respectively). The seniority of prescriber was significantly associated with the appropriateness of prescriptions (P < 0.05). Antibiotics prescription was higher in cold/cough and diarrhea (93.5%) in comparison to cough/cold (85%) or diarrhea (75%) alone. CONCLUSIONS: The study observed high rates of antibiotic utilization in Chidambaram during the treatment of cough/cold and/or diarrhea in pediatric patients. The findings highlight the need for combined interventions using education and expert counseling, targeted to the clinical conditions and classes of antibiotic for which inappropriate usage is most common.

Synthesis and evaluation of MePEG-PCL diblock copolymers: surface properties and controlled release behavior.

The amphiphilic block copolymers are composed of various combinations of hydrophilic and hydrophobic block unimers. The variation in unimer ratio alters the surface as well as micelle-forming properties of the block copolymers. These nanoscopic micelles have the ability to encapsulate hydrophobic compounds and act as potential drug carrier. MePEG-PCL copolymers with various block lengths were synthesized by ring-opening polymerization and characterized by 1HNMR, GPC, WXRD and DSC. The number average molecular weight of the block copolymer was found to vary from 7511 to 21,270 as determined by GPC and 1HNMR studies. The surface topology of the polymer films was determined by AFM analysis, which shows a smoother surface with increased MePEG contents in the block copolymers. The protein-binding assay indicates a better biocompatibility of the block copolymers in comparison to MePEG or PCL alone. The CMC of the block copolymer provides the information about micelle formations for encapsulation of hydrophobic materials and affects the in vitro release.

Micelle-assisted combination therapies for effective glioblastoma treatment: an in-vitro assessment.

Glioblastoma is the most fatal type of brain tumor, requiring a better chemotherapy regime to prolong the survival of the patient. The toxicity associated with a high dose of a single drug can be overcome by a combination of different anticancer drugs. Methoxy poly(ethylene glycol)-poly (ε-caprolactone) block copolymeric micelles loaded with two different anticancer drugs such as curcumin and rapamycin were used to assess their therapeutic efficacy in glioblastoma cell lines. In addition, the combination of curcumin and rapamycin was also encapsulated in micelles for better anticancer activity. The in-vitro cellular uptake studies and cytotoxicity studies showed that the drugs encapsulated in the micelles showed ∼3.3 times more uptake than a mixture of native drugs as well as a single drug. The enhanced mitochondrial membrane potential depolarization by drug-loaded micelles leads to higher cell death compared with native drugs in T98G glioblastoma cell culture experiments. The drug combination downregulates P13/AKT and serine/threonine kinase proteins, and leads to programmed cell death. Thus, curcumin and rapamycin-loaded micelles can be used effectively for the treatment of glioblastoma.

Preparation and characterization of nebivolol nanoparticles using Eudragit® RS100.

Nebivolol, a beta-blocker, has been widely used for the treatment of hypertension and cardiovascular diseases; but has drawbacks like poor solubility and bioavailability requiring frequent dosing. The present study attempts to overcome these issues through nanoparticulate delivery system using widely used carrier Eudragit(®) RS100. The solvent evaporation (single emulsion) technique was used for developing nanoparticles. The impact of formulation and process variables on particle size and entrapment efficiency was studied to optimize the formulation. The physico-chemical characterization confirmed the particle size in nano range with smooth and spherical morphology. Further, Fourier transforms infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies confirm compatibility of drug-polymer combination. The in vitro drug release study of the prepared nanoparticles showed prolongation of drug release with reduced burst release in comparison with pure drug powder.

The role of pharmacoeconomics in current Indian healthcare system.

Phamacoeconomics can aid the policy makers and the healthcare providers in decision making in evaluating the affordability of and access to rational drug use. Efficiency is a key concept of pharmacoeconomics, and various strategies are suggested for buying the greatest amount of benefits for a given resource use. Phamacoeconomic evaluation techniques such as cost minimization analysis, cost effectiveness analysis, cost benefit analysis, and cost utilization analysis, which support identification and quantification of cost of drugs, are conducted in a similar way, but vary in measurement of value of health benefits and outcomes. This article provides a brief overview about pharmacoeconomics, its utility with respect to the Indian pharmaceutical industry, and the expanding insurance system in India. Pharmacoeconomic evidences can be utilized to support decisions on licensing, pricing, reimbursement, and maintenance of formulary procedure of pharmaceuticals. For the insurance companies to give better facility at minimum cost, India must develop the platform for pharmacoeconomics with a validating methodology and appropriate training. The role of clinical pharmacists including PharmD graduates are expected to be more beneficial than the conventional pharmacists, as they will be able to apply the principles of economics in daily basis practice in community and hospital pharmacy.

Preparation and evaluation of a new erythromycin derivative -- erythromycin taurate.

Erythromycin taurate, a new derivative of erythromycin, was prepared by reacting erythromycin base with tauric acid and its physico-chemical and biological properties were evaluated. The derivative has reasonably good solubility in organic solvents. The partition coefficient values in chloroform/water 1.17 and octanol/water 1.16 systems indicate its good distribution in various tissues in vivo. The in vitro antimicrobial potency of the derivative (833.33 microg mg(-1)) is higher than that of the existing derivatives such as erythromycin estolate, erythromycin stearate, erythromycin ethyl succinate, erythromycin gluceptate, erythromycin lactobionate. The antimicrobial spectrum is comparable to that of the parent compound. Our results indicate that erythromycin taurate has a high potential for possible clinical application and is more efficient against Escherichia coli and Klebsiella pneumoniae than the parent base.