Development, physical characterization, micromeritics and in vitro release kinetics of letrozole loaded biodegradable nanoparticles.

The present investigation was aimed at preparing and characterizing biodegradable nanoparticles of letrozole with poly (D,L-lactide-co-glycolide) monomer ratio 50:50. The nanoparticles were prepared by direct precipitation technique. Different formulations were prepared by changing polymer-drug ratio at two different levels of phase volume ratio. The prepared nanoparticles were evaluated for the recovery, drug entrapment efficiency, micromeritic properties and particle size distribution profile, surface morphology and in vitro release kinetics. The results show that the nanoparticles recovery and drug entrapment efficiency vary from 37 to 79% and 12 to 27% respectively. Span value and mean diameter (MD) of different formulations were found to vary from 0.937 to 2.462 and 146 nm to 267 nm, respectively. Field Emission Scanning Electron Microscopy (FESEM) revealed the particles to be spherical with smooth surfaces. Release kinetics fitted the Higuchi model and ensured the capability of sustaining the drug release from the nanoparticles.

Development and validation of a spectrophotometric method for estimation of letrozole in bulk and pharmaceutical formulation.

A simple, sensitive and accurate UV spectrophotometric method has been developed for the determination of letrozole, a new aromatase inhibitor, in raw material and tablets. The drug shows maximum absorption at 238 nm. Beer's law was obeyed in the concentration range 2-20 microg/mL for the drug. Results were validated statistically according to ICH guidelines. Validation of the method yielded good results concerning range, linearity, precision and accuracy. It was found that the excipients present in the commercial formulation did not interfere with the method.

Release and skin permeation studies of Naproxen from hydrophillic gels and effect of terpenes as enhancers on its skin permeation.

The skin permeation parameters of Naproxen through albino mouse abdominal skin was investigated. Out of 5 formulations those prepared from carbomer gels showed promising results and were chosen for investigating enhancing effect of various terpene alcohol viz. Geraniol and Nerolidol and cyclic terpenes viz menthol and thymol on skin permeation of Naproxen. Out of the four terpenes studied Geraniol exhibited the highest enhancing effect with enhancement ratio 4.6, while Nerolidol had an enhancement ratio 4.2. The cyclic terpenes had less prompt enhancing effect compared to the alcohol terpenes, out of the two, methol showed the largest effect with an enhancement ratio of about 3.7 and thymol had an enhancement ratio of 3.5.

Effect of hydrophobic permeation enhancers on the release and skin permeation kinetics from matrix type transdermal drug delivery system of ketotifen fumarate.

Ketotifen fumarate is effective in low doses in the treatment of bronchial asthma particularly of allergic origin. However, it is substantially metabolized in the liver when administered orally. Hence transdermal patches of combination of ethylcellulose/polyvinylpyrrolidone and Eudragits RS 100/RL 100 were prepared and their drug release kinetics and skin permeation profiles were evaluated. However, the skin permeation profiles were found to be low and subtherapeutic. Hence three hydrophobic biocompatible substances, viz, isopropyl myristate, isopropyl palmitate and linoleic acid and also combination of isopropyl myristate and linoleic acid were used as permeation enhancers in the film. It was found that isopropyl myristate and linoleic acid combination and isopropyl myristate alone produced promising results compared to isopropyl palmitate and linoleic acid.

Permeation kinetics of ketotifen fumarate alone and in combination with hydrophobic permeation enhancers through human cadaver epidermis.

Permeation kinetics for ketotifen fumarate from transdermal system through hairless mice skin and hog skin have been reported. However, permeation of ketotifen fumarate through human skin is not available till date. In view of the above, permeation profile and related kinetic parameters of ketotifen fumarate alone and in presence of three compatible enhancers namely Myristic acid isopropyl ester, Palmitic acid propyl ester and Lauric acid propyl ester through normal and delipidized human cadaver have been reported in the present study. The observed permeability flux, permeation coefficient and epidermal partition coefficient through 50% dried human cadaver epidermis were found to increase in presence of the three enhancers, amongst which the effect was found to be maximum with Myristic acid isopropyl ester. The more pronounced enhancing effect of Myristic acid isopropyl ester regarding permeability flux, permeation coefficient, epidermal partition coefficient and diffusion coefficient was attributed with solubility parameter being nearer to the skin lipid solubility parameter and probably due to its passage across the skin barrier through the lipid pathway.

Nonionic surfactant vesicles (niosomes) of cytarabine hydrochloride for effective treatment of leukemias: encapsulation, storage, and in vitro release.

Niosome vesicles of cytarabine hydrochloride were prepared by a lipid hydration method that excluded dicetylphosphate. The sizes of the vesicles obtained ranged from 600 to 1000 nm, with the objective of producing more blood levels in vivo. The study of the release of drug from niosomes exhibited a prolonged release profile as studied over a period of 16 hr. The drug entrapment efficiency was about 80% with Tween 80, Span 60 and Tween 20; for Span 80, it was 67.5%. The physical stability profile of vesicular suspension was good as studied over a period of 4 weeks.

Some biochemical properties of Russell's viper (Daboia russelli) venom from Eastern India: correlation with clinico-pathological manifestation in Russell's viper bite.

In the present study, some biochemical properties and pathological effects of Daboia russelli venom from Burdwan district of West Bengal, eastern India are presented. The clinical features of Russell's viper envenomation observed in patients admitted to Burdwan Medical College & Hospital are also reported. In vitro, whole venom exerts strong trypsin inhibitory, phospholipase A2 and procoagulant activities in addition to moderate adenosine monophosphatase and adenosine triphosphatase activities. Lethality (LD50) of this venom sample is 0.7 mg kg (i.v.) of mice. Significant local tissue damaging effects including edema, hemorrhage and necrosis are observed in experimental animal models. An increase in the level of serum enzymes, such as aspartate transaminase, alkaline phosphatase, creatine phosphokinase, lactate dehydrogenase after D. russelli venom injection in albino rats is indicative of cell or tissue damage. High incidence of intravascular hemolysis in addition to hemostasis, haemoptysis and haematuria are observed as the most prominent features of RVV envenomation from this part of India. The present study reinforces the hypothesis that variation in the venom composition of RVV from eastern India with respect to venom samples of Russell's vipers from other parts of India is responsible for the differences in the clinical manifestation in patients from eastern India.

Assessment of bioavailability of experimental controlled release microcapsules of nifedipine.

Experimental controlled release nifedipine microcapsules composed of ethylcellulose and eudragit RL were explored for the assessment of bioavailability on rabbit. The pharmacokinetic parameters were compared between the formulations and with the pure drug material. A statistically significant difference between the formulations was noticed in the parameters, K, T1/2, AUC (0-->infinity), MRT and bioavailability but not in Vd, Cmax and Tmax and in each case a highly significant difference was observed with reference drug material. Controlled release absorption profiles in vivo were observed from the experimental microcapsules as revealed by the Wagner-Nelson method. The absorption lag time, absorption rate constant, and absorption half life were calculated by using the back projection method of residuals. A good correlation demonstrated between in vivo absorption and in vitro release data for both the products merits specific attention. There was no loss in bioavailability of the experimental ethylcellulose microcapsule (drug content 75.8%), even though nifedipine undergoes extensive first pass metabolism.

Effect of oral supplementation of vitamin E on the hemolysis and erythrocyte phospholipid-splitting action of cobra and viper venoms.

In the present investigation, it was found that oral supplementation of graded amounts of vitamin E to volunteers increased the alpha-tocopherol content of the erythrocytes and decreased the susceptibility of the latter to the hemolytic action of cobra and viper venoms. Further, exogenous addition of graded amounts of alpha-tocopherol to the red cells, prior to the addition of either venoms, minimizes the venom-induced lysis and erythrocyte phospholipid splitting. It may thus be inferred that vitamin E, a fat-soluble antioxidant, plays an important role in reducing the hemolytic action of cobra and viper venoms.

Lysosomal membrane stabilization by alpha-tocopherol against the damaging action of Vipera russelli venom phospholipase A2.

This investigation shows the membrane stabilizing effect of alpha-tocopherol against the damaging action of viper venom phospholipase A2 (PLA2). Liver lysosomal membranes from rats fed 100 mg and 200 mg alpha-tocopherol acetate per kilogram of diet were more resistant to damage by viper venom PLA2 compared with vitamin E-deficient rats. The membrane stabilizing effect of vitamin E is proposed to be due to the formation of a complex with the phospholipid hydrolysis products of the membrane.

In-vitro binary release kinetics of sulphamethoxazole and trimethoprim microcapsules.

Sulphamethoxazole and trimethoprim are separately microencapsulated with polyacrylic resin: Eudragit RS 100. The data so obtained from the drug release have been analyzed according to the different existing kinetic models (1) Zero order (2) First order and (3) Higuchi Matrix Kinetics. It is observed that in both the cases of single component and binary release of sulphamethoxazole (SMZ) and trimethoprim (TMP), Higuchi mechanism predominates. Lastly, a comparative study is made between The Single and Binary release kinetics to correlate the diffusivity rate constant (KBL) and diffusion Coefficient (Da) which have been estimated according to Baker-Lonsdale method at pH 1.2.

Mechanism and pathway of glucose transportation in a digenetic trematode Ceylonocotyle scoliocoelium.

The mode of absorption, kinetics and mechanism of transportation of 14C--glucose in a digenetic trematode, Ceylonocotyle scoliocoelium were studied by culturing the trematodes under in vitro condition in Hank's saline supplemented with radioactive tracer. It was then followed separately by autoradiography and liquid scintillation. Autoradiographic study reveals that the maximum amount of glucose uptake occurs through cuticle whereas the role of intestinal canal is insignificant in this respect. Maximum cpm is recorded in the precipitate followed by TCA treatment. This is due to the presence of a protein-bound 14C-glucose which is assumed as the carrier protein. The inhibitor, phlorizin, used here presumably acts noncompetitively.

Duration of meiosis and spermiogenesis in the dog.

The duration of meiosis and spermiogenesis was studied in the dog by following the kinetics of [3H]thymidine-labeled canine spermatocytes autoradiographically. Leptotene appears to last for at least 4.20 days, zygotene for less than a day, and pachytene for about 15.50 days. The transition from diplotene to metaphase II is extremely rapid and requires approximately a day. The duration of spermiogenesis is at least 19.60 days. Both meiosis and spermiogenesis are completed by 42.15 days.