ABSTRACT

Due to the lower risk of systemic side effects topical treatment of skin disease appears favourable, yet the stratum corneum counteracts the penetration of xenobiotics into viable skin. Fatty acids have been widely used as adjuvant, vehicles in drug delivery viz penetration enhancers in topical delivery and in polymeric micelles to provide sustained release. However, the present investigation aims at exploring the potential of fatty acid vesicles for the topical delivery of 5-FU. Vesicles were prepared by film hydration method using oleic acid as a fatty acid principal component. Developed vesicles were characterized for size, size distribution, shape, In vitro release, pH dependent and storage stability, skin and ex-vivo skin permeation. Optical microscopy and TEM studies confirmed vesicular dispersion of fatty acid. The vesicles possessed higher entrapment efficiency (64.0±4.2%) with optimum vesicle size and homogeneity in regard to size distribution (PDI = 0.234 ± 0.016) at 7:3 oleic acid-to-5-FU ratio. In vitro drug release study suggested sustained release of drug from the vesicles. The vesicles were fairly stable at refrigerated conditions. Ex-vivo skin permeation and Confocal microscopic studies suggested that oleic acid vesicles penetrate the stratum corneum and retain the drug accumulated in the epidermal part of the skin. On the basis of sustained release behavior and skin retention it can be inferred that oleic acid vesicles can serve as a potential carrier for the topical localized delivery of bioactives.

Key words: Oleic acid, 5-FU, CLSM

ABSTRACT

Present work is about the development of bioanalytical method of estimation for an atypical antipsychotic drug Olanzapine from endogenous matrix. Olanzapine is an atypical antipsychotic drug that chemically belongs to thieno benzodiazepine derivative. Bioanalytical estimation of antipsychotic drugs has clinical significance because of probable drug accumulation in body tissues because of long term treatment regime. Olanzapine has been recommended as the first-line drug for the treatment of schizophrenia. It is considered an atypical neuroleptic agent with fewer extrapyramidal side effects than classical neuroleptic agents. In the study initially an alternative bioanalytical estimation method, with the added advantages of decreased run time and minimization of endogenous matrix interferences was developed, which is indicated by high degree of specificity. Developed method was validated for quantization of drug Olanzapine. Developed method was finally cross validated for the estimation of Olanzapine after multiple dosing of drug in experimental animal. Result of study revealed linear detector response from 100 –500 ng/ml, with the correlation coefficient (r² =0.989). The limit of detection and limit of quantification of the assay were 27.76 ng/ml and 79.96 and 78.55% ng/ml respectively. The recoveries of Olanzapine from plasma and brain tissue were found to be 79.96 % w/v and 78.55% w/v respectively. The applicability of the assay was confirmed for multiple dose drug determination in blood plasma and brain tissue of Olanzapine in wistar rats after i.p. administration for 10 consecutive days. This method is suitable for studying Olanzapine pharmacokinetics and toxico-kinetics in single or multiple-dose studies.

Key words: Olanzapine, Bioanalytical, High Performance Liquid Chromatography.

ABSTRACT

The present work reports the study of different Lamivudine (LAM): excipient formulations, in order to determine the effect of the polymer substitution and type of diluents on the drug-release mechanism. Seven formulations were prepared using either HPMC K15M alone or in combination with Ethyl Cellulose (EC). Release kinetics was evaluated by using United States Pharmacopeia (USP)-22 type I dissolution apparatus. The tablets were tested for their drug content, weight variation, hardness, thickness, tensile strength, friability, swelling and release ratio. Polymers HPMC K15M was found not to be appropriate for the preparation of modified release LAM hydrophilic matrix tablets, while combination of HPMC K15M and EC showed to be advantageous. The analysis of the release profiles in the light of distinct kinetic models (zero-order, first-order, Higuchi and Korsmeyer–Peppas) led to the conclusion that the concentration of polymer did not influence the release mechanism of the drug. The mean dissolution time (MDT) and t₅₀% was determined, the highest MDT and t₅₀% value being obtained for HPMC and EC formulations. Moreover, the drug-release process was not found to be influenced by the type of diluents, either MCC or DCP.

Key words: Lamivudine, HPMC, Ethyl Cellulose

ABSTRACT

Fifteen new Fluorine substituted Schiff bases were prepared by condensation of different substituted benzaldehyde with 4-fluoroaniline. The structures of these Schiff bases have been confirmed by IR, ¹H NMR, mass and elemental analysis. All the new compounds synthesized have been evaluated for their action against bacteria and fungi.

Key words: Schiff bases, 4-fluoroaniline, substituted benzaldehyde, antimicrobial activity.

ABSTRACT

Nimodipine is an antihypertensive, calcium channel blocker, vasodilator agent and used in the treatment of various cardiovascular disorders such as angina pectoris, cardiac arrhythmia and hypertension. Oral bioavailability of Nimodipine is around 13% and having half life 9 hrs. In present research work an attempt has been made to prepare fast dissolving tablets of Nimodipine by direct compression technique with β-cyclodextrin complexes using various superdisintegrants. The powder blends were subjected for pre-compressional parameters. The prepared tablets were evaluated for post-compressional parameters. The prepared tablets were characterized by DSC and FTIR Studies. No chemical interaction between drug and excipients was confirmed by DSC and IR studies. The values of pre-compression parameters evaluated were within prescribed limits and indicated good free flowing property. All the post-compressional parameter are evaluated were prescribed limits and results were within IP acceptable limits. The tablets were evaluated for the in-vitro disintegration time and it was observed that the time for all the formulations varied from 19.24 to 48.29 sec. The promising formulations CCP₄, CCC₄ and CSS₁ shows the 90 % of drug released within 5-8 min. Among all the formulation CCP₄ (15 % crospovidone) were found to be best and showed a disintegration time of 19.24 sec, 50 % of drug released in 0.96 min, and 90 %  of drug released in 4.78 min. The stability study was conducted as per the ICH guidelines and the formulations were found to be stable, with insignificant changes in hardness, drug content and disintegration time. These results revealed that fast dissolving tablets of the poorly soluble drug, Nimodipine, showing enhanced dissolution and, hence, better patient compliance.

Key words: Fast dissolving tablets, Nimodipine, sodium starch glycolate, croscarmellose sodium, crospovidone,  β-cyclodextrin.

ABSTRACT

A simple, sensitive and rugged quantitative method for the determination of Clopidogrel in human plasma (K₂EDTA) using liquid chromatography-tandem mass spectrometric (LC-MS/MS) method has been developed and validated. Clopidogrel-d₃ was used as an internal standard. Analyte and the internal standards were extracted from human plasma by liquid-liquid extraction technique using Methyl tertiary butyl ether as extraction solvent and 0.5% formic acid as extraction buffer. The reconstituted samples were chromatographed on a C18 column by using acetonitrile / 5mM ammonium acetate (90/10, V/V) as the mobile phase. The method was validated over the concentration range of 101.98–61028.96 pg/mL. The Quattro Premier XE mass spectrometry was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique for quantification of ion transitions at m/z 322.13/212.04 and 326.06/215.04 for the drug and the internal standard respectively. The results of the intra and inter batch precision and accuracy studies were well within the acceptable limits. The method has been proved to be simple, sensitive, fast, reliable, rugged and reproducible. A run time of 2.50 min for each sample made it possible to analyze more than 400 plasma samples per day. The proposed method can be applied for the estimation of the drug in real time plasma samples for pharmacokinetic studies.

Key words: Clopidogrel, Validation, Human Plasma, LC-MS/MS, Electrospray ionization.

ABSTRACT

Benzo(a) pyrene (BP), the polycyclic aromatic hydrocarbon which is highly carcinogenic present in tobacco smoke causes lung cancer. So nowadays a lot of attention on plant based products which act as chemopreventive agents are used to prevent lung cancer. So the present investigation focuses on the Punica granatum which is a medicinal plant and used in folk medicines. The present investigation was carried out to determine the effect of ethyl acetate fraction of Punica granatum rind extract on tumor markers in benzopyrene induced lung cancer in Swiss albino mice. The analysis on tumor markers revealed that the ethyl acetate fraction of Punica granatum rind extract possess antineoplastic effect on lung cancer induced in Swiss albino mice which may be due to the highest percentage of Pyrogallol in the active fraction.

Key words: Punica granatum, Benzopyrene, Swiss albino mice, Lung cancer, Pyrogallol.

ABSTRACT

Rapid and accurate High performance liquid chromatography method is described for Simultaneous estimation of Metformin Hydrochloride and Sitagliptin Phosphate from the combination tablet dosage form. The separation of two drugs was achieved on HYPERSIL (250 x 4mm i.d) 5μ column. The mobile phase consists of Acetonitrile and phosphate buffer in the ratio of 45:55. The detection was carried out at a wavelength 260nm. The method was validated for system suitability, linearity, accuracy, precision, robustness and stability of sample solution. The linear ranges for Metformin Hydrochloride and Sitagliptin Phosphate were 20-120μg/mL, 2-12μg/mL respectively with good recoveries i.e. 99.16% to 99.89%.

Keywords: Metformin hydrochloride, Sitagliptin phosphate, High performance liquid chromatography. 

ABSTRACT

Osteoporosis is major problem in women and geriatric patients where antiresorptive agents are normally recommended. Bisphosphonates (BPs), which have proven efficacy in terms of bone resorption reduction, increase of bone in mineral density, and reduction in fracture risk. Although the oral bioavability of Bisphosphonates is low, their clinical efficacy favors oral administration. Currently marketed oral bisphosphonates preparations suffer from the drawback of discontinuation of therapy due to side effects. This paper provides a comprehensive review of literature on various approaches and technologies attempted to improve the bioavailability and reduce gastric intolerance of oral bisphosphonates. Simultaneously future opportunities for oral delivery of bisphosphonates are also examined.

Key words: Bisphosphonates, side effects, poor oral bioavailability, approaches, patented technology, future opportunities.

ABSTRACT

The worldwide CNS pathology incidence displayed that about 1.5 billion people suffer from CNS disorders. The worrying  fact that , delivering drugs to the CNS is impaired by the presence of the blood-brain barrier (BBB) that represents the main obstacle for CNS drug development, many hydrophilic drugs and neuropeptides etc are may have difficulty in crossing the blood-brain barrier. It is important to consider not only the net delivery of the agent to the CNS, but also the ability of the agent to access the relevant target site within the CNS. Many strategies have been developed to deliver the drug into brain by crossing the BBB are chemical delivery systems, magnetic drug targeting, or drug carrier systems such as antibodies, liposomes or Nanoparticles. Among those, Nanoparticles have got a great concentration as the potential targeted drug delivery systems in the brain recently. Nanoparticles (NP) are solid colloidal particles ranging in size from one to 1000nm that may be utilized as brain drug delivery carriers. Coating of Nanoparticles with drug molecules are as carriers to cross the BBB and transport the drugs to the specific sites in brain where they are needed.  NPs may provide slow drug release in blood and thereby reduces the peripheral toxicity.

Key words: BBB, Drug delivery to brain, Nanotechnology, Colloidal drug carriers.

ABSTRACT

Buccal delivery is considered to be an important alternative to the peroral route for the systemic administration of  drugs. The paper describes formulation of buccal mucoadhesive gel from Ficus carica mucilage using prorpranolol hyderochloride. Propranolol, a nonselective beta adrenergic blocking agent, has been widely used in the treatment of hypertension, angina pectoris, and many other cardiovascular disorders. It is highly lipophilic and is almost completely absorbed after oral administration. However, much of the drug is metabolized by the liver during its first passage through the portal circulation; on average, only about 25% reaches the systemic circulation. The conventional oral dosage form of this drug has low bioavailability due to high first pass metabolism, so it is modified as buccal drug dosage form to improve bioavailability and for the localized drug release because of high vascularity and drugs diffusing across the membrane have easy access to the systemic circulation via internal jugular vein. In present research mucilage is extracted from Ficus carica and studeuied for there mucoadhesive properties. The gel were evaluated by different parameters such as zeta potential, viscosity, Gel strength, Drug Release, Mechanism of drug release & histological study.

Keyword: Buccal delivery, mucoadhesive, Ficus carica mucilage