Formulation, Optimization, and Characterization of Repaglinide Loaded Nanocrystal for Diabetes Therapy

The aim of the present investigation was to formulate and characterize nanocrystal formulation of Repaglinide for diabetes therapy. Formulation was done by high pressure homogenization. HPH pressure and cycles range were screened by preliminary batches (T1 and T2). 5, 8, and 10 cycles and 500 to 1500 bar pressure range had kept for further investigation. Taguchi design was used to optimize type of polymer, % polymer concentration, number of cycles, and HPH pressure for nanocrystal formulation. Formulations were characterized for particle size, zeta potential, and in vitro drug release. Optimized formulation (NC 3) showed particle size of 187 nm, zeta potential of −29.4 mv, and % drug release of 80.58% and it was used for further study. Data analysis proved significant effects of factors on responses. Polydispersity index (PDI) Analysis of optimized formulation were found to be 0.248. SEM showed nanocrystal aggregation of drug, may be due to water removal process. DSC showed slight change in crystallinity, may be due to the presence of PEG 4000. Stability study was carried out for 3 months. It indicated no significant change in particle size and zeta potential. However, further studies in higher animals and human being need to be performed before this formulation can be commercially exploited.

Acute and Subchronic Toxicity Profile of Euphorbia pulcherrima Methanol Extract on Wistar Albino Rats

This work was designed to evaluate the acute and subchronic toxicity of E. pulcherrima methanol extract. Mean lethal dose (LD50) and subchronic toxicity were determined using Lorke’s method to assess the effect of the extract on kidney and liver functions along histopathology assessment of the liver and kidney, respectively. The LD50 determined was 3807.89 mg/kg both orally and intraperitoneally. The kidney function parameters indicated elevation of the serum urea above the normal value in both control and the group treated with 10 mg/kg of the extract with mean values of 7.92 ± 1.19 and 7.86 ± 1.14 mMol/L, respectively. The creatinine and electrolytes were within the normal values. The results of ALAT, ASAT, ALP, T protein albumin, and bilirubin in all cases were within the normal values. Kidney, liver function parameters, and relative organ weight were statistically insignificant across all groups. This shows that various concentrations of E. pulcherrima extract did not influence negatively the liver and kidney function parameters. Further studies are required to rule out the observed mild hepatic histological changes among a few members of the groups treated with 100 and 1000 mg/kg/day and any possible hepatoprotective and nephron-protective potential the extract may possess.

Determination of Glycerin from a Marketed Personal Care Product Using Gas Chromatography

The current study presents a packed column gas chromatographic technique for the estimation of glycerin using a flame ionization detector from a marketed hair tonic in presence of resorcinol, ethanol, biotin, keratin hydrolysate, undecylenic acid alkylolamide (hyalkyl HBU), D-biotin, nicotinic acid, and polyvinylpyrrolidone. The validation studies show the proposed method to be specific, sensitive, precise, and accurate. The method is found to be linear in the concentration range 1.25 mg/mL to 10.02 mg/mL with r2 value 0.99. The limit of detection and the limit of quantitation were 0.01 mg/mL and 0.05 mg/mL, respectively. The method does not involve any complex sample preparation procedure and is therefore suitable for regular analysis of glycerin from marketed hair tonic.

Unresponsiveness of Experimental Canine Leishmaniosis to a New Amphotericin B Formulation

This study was designed to evaluate the efficacy and safety of a novel free polyaggregated amphotericin B (FPA) formulation used to treat experimental canine leishmaniosis (CanL) caused by Leishmania infantum. Eight healthy beagles were intravenously challenged with 5×107 promastigotes per mL of L. infantum. One year after infection, they received an intravenous dose of FPA (5 mg/kg) every 2 weeks three times. Dogs were assessed monthly for clinical signs, serology, and parasite detection during a follow-up period of 6 months. Transient adverse effects (i.e., hypotension, diarrhea, bodyweight loss, fever, and asthenia) were observed within 24–48 hours after treatment in 4 animals. In three dogs mean clinical signs scores were reduced. Antibody titers measured by immunofluorescence antibody test (IFAT) had significantly diminished at the end of the study, although according to bone marrow smears and cultures a high percentage of dogs tested positive for the parasite at 6 months posttreatment (PT6). Real-time quantitative PCR (rtQ-PCR) on blood, bone marrow, and urine samples revealed the presence of parasitic DNA in all animals at PT6, although blood loads of the parasite were reduced. These findings indicate that FPA at the dosing regimen used did not achieve clinical or parasitological cure in dogs experimentally infected with L. infantum.

A Comprehensive Review on Dry Eye Disease: Diagnosis, Medical Management, Recent Developments, and Future Challenges

Dry eye syndrome (DES) or keratoconjunctivitis sicca (KCS) is a common disorder of the tear film caused by decreased tear production or increased evaporation and manifests with a wide variety of signs and symptoms. The present review from interpretation of the literature gives detailed information on the prevalence, definition, causes, diagnostic tests, and medical management of dry eye disease. A number of systems contribute to the physiological integrity of the ocular surface and disruption of system may or may not produce symptoms. Therefore accurate diagnosis of dry eyes with no or minimal disruption of physiological function is necessary. The paper also discusses different colloidal drug delivery systems and current challenges in the development of topical ophthalmic drug delivery systems for treatment of KCS. Due to the wide prevalence and number of factors involved, newer, more sensitive diagnostic techniques and novel therapeutic agents have been developed to provide ocular delivery systems with high therapeutic efficacy. The aim of this review is to provide awareness among the patients, health care professionals, and researchers about diagnosis and treatment of KCS and recent developments and future challenges in management of dry eye disease.

Enhanced Degradation of Lactide-co-Glycolide Polymer with Basic Nucleophilic Drugs

The purpose of this study was to examine the degradative effect of weakly basic nucleophilic drugs on a lactide-co-glycolide (PLGA) polymer in a microsphere formulation. Biodegradable PLGA microspheres of two second-generation atypical antipsychotics, Risperidone and Olanzapine, were manufactured using a solvent extraction/evaporation technique. The effect of drug content, buffer pH and temperature on polymer molecular weight and degradation, were examined via a series of experiments and compared against a control (Placebo PLGA microspheres). In comparison to Placebo microspheres, significant polymer molecular weight reduction was observed upon encapsulation of varying levels of either Risperidone or Olanzapine. There was excellent correlation between the extent of molecular weight reduction during manufacture and the amount of encapsulated drug in the microspheres. Subsequent studies on polymer degradation showed: the following (a) the Placebo and Olanzapine microspheres followed pseudo first order kinetics, (b) Risperidone microspheres exhibited biphasic degradation profiles, and (c) polymer degradation was dependent on temperature, not pH. The findings of these studies show that encapsulation of weakly basic nucleophile type drugs into PLGA can accelerate the biodegradation of the PLGA and have major implications on the design of polymeric microsphere drug delivery systems.

Formulation Development of Mouth Dissolving Film of Etoricoxib for Pain Management

Etoricoxib is a potent, orally active, and highly selective COX-2 inhibitor that exhibits anti-inflammatory, analgesic, and antipyretic activities. The present research was undertaken to develop mouth dissolving films of etoricoxib to have rapid onset of action. Mouth dissolving film (MDF) is a better alternate to oral disintegrating tablets due to its novelty, ease of use, and the consequent patient compliance. Solubility enhancement and taste masking of etoricoxib were the two challenges solved by formulating drug-inclusion complex with beta-cyclodextrin (BCD). MDF prepared by solvent casting etoricoxib-BCD complex along with HPMC as film forming polymer was found to possess desirable physicomechanical properties. In vitro release of etoricoxib from MDF in simulated salivary fluid and 0.1 N HCl was more than 95% within 2 minutes. Taste masking and in vivo disintegration were in acceptable range as assessed by human volunteers. Etoricoxib MDF was further characterized by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy. The index of analgesia shown by etoricoxib MDF was comparable to that of immediate release tablets (100% activity within 40 minutes) in animal studies. Conclusively, the present study documents the development of a commercially viable formula for an MDF of etoricoxib with rapidity in pain management.

Preliminary Investigation of Bioactive Compounds and Bioautographic Studies of Whole Plant Extract of Euphorbia pulcherrima on Escherichia coli, Staphylococcus aureus, Salmonella typhi, and Pseudomonas aeruginosa

The aim of this study is to carry out preliminary investigation of bioactive compounds and bioautographic studies of whole plant extract of Euphorbia pulcherrima on Escherichia coli, Staphylococcus aureus, Salmonella typhi, and Pseudomonas aeruginosa. Tukey HSD test of hierarchy for the effect of different solvents crude extract on bacterial isolates indicates the methanol extract as the most bioactive. The Tukey HSD analysis also showed that the bioactivities of the crude extracts of the various parts of Euphorbia pulcherrima were part dependent and the whole plant was the most bioactive. The ethyl acetate fraction of the methanol extract of the whole plant of Euphorbia pulcherrima has been shown in this work to contain phytochemicals which have shown remarkable activities against Escherichia coli, Staphylococcus aureus, Salmonella typhi, and Pseudomonas aeruginosa. The bioactivities against the test organisms were due to the combined effects of the compounds separated on TLC plates. Families of terpenoids, flavonoids, alkaloids, saponin, and steroids that were detected in the extracts were identified by GC-MS. The various classes of phytochemicals in the E. pulcherrima plant provided the antimicrobial potency of the plant.

Unstirred Water Layer Effects on Biodegradable Microspheres

This study explores the mechanistic aspects of in vitro release from biodegradable microspheres with the objective of understanding the effect of the unstirred water layer on polymer degradation and drug release. In vitro drug release experiments on Leuprolide PLGA microspheres were performed under “static” and “continuous” agitation conditions using the “sample and separate” method. At specified time intervals, polymer degradation, mass loss, and drug release were assessed. While molecular weight and molecular number profiles for “static” and “continuous” samples were indistinct, mass loss occurred at a faster rate in “continuous” samples than under “static” conditions. In vitro results describe a fourfold difference in drug release rates between the “continuous” and “static” samples, ascribed to the acceleration of various processes governing release, including elimination of the boundary layer. The findings were confirmed by the fourfold increase in drug release rate when “static” samples were subjected to “continuous” agitation after 11 days. A schema was proposed to describe the complex in vitro release process from biodegradable polymer-drug dosage forms. These experiments highlight the manner in which the unstirred water layer influences drug release from biodegradable microspheres and stress the importance of selecting appropriate conditions for agitation during an in vitro release study.

Development and Validation of Acyclovir HPLC External Standard Method in Human Plasma: Application to Pharmacokinetic Studies

A simple, rapid, and selective RP-HPLC method was developed for the estimation of acyclovir in human plasma. The method involves a simple protein precipitation technique. Chromatographic separation was carried out on a reverse phase C18 column using mixture of 5 mM ammonium acetate (pH 4.0) and acetonitrile (40 : 60, v/v) at a flow rate of 1.0 mL/min with UV detection at 290 nm. The retention time of acyclovir was 4.12 minutes. The method was validated and found to be linear in the range of 25.0–150.0 ng/mL. Validation studies were achieved by using the fundamental parameters, including accuracy, precision, selectivity, sensitivity, linearity and range, stability studies, limit of detection (LOD), and limit of quantitation (LOQ). It shows recovery at 91.0% which is more precise and accurate compared to the other method. These results indicated that the bioanalytical method was linear, precise, and accurate. The new bioanalytical method was successfully applied to a pharmacokinetic linearity study in human plasma.