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Table of Contents
July-September 2011
Volume 3 | Issue 3
Page Nos. 171-258
Online since Saturday, August 13, 2011
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PHARMACEUTICS
Design of vitamin E D-
α
-tocopheryl polyethylene glycol 1000 succinate-emulsified poly (D,L-Lactide-co-glycolide) nanoparticles: Influence of duration of ultrasonication energy
p. 171
CT Sengel, C Hasçiçek, N Gönül
DOI
:10.4103/0975-1483.83754
The aim of this research was to investigate the effect of the duration of ultrasonication energy on the physicochemical characteristics of the nano-sized particulate drug delivery systems. For this purpose, meloxicam-loaded vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-emulsified poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles were designed by using ultrasonication-solvent evaporation technique and were characterized by photon correlation spectroscopy for size and size distribution, scanning electron microscopy for surface morphology and laser Doppler anemometry for surface charge. Ultraviolet -spectrophotometer was used to measure the drug encapsulation efficiency and to obtain
in vitro
drug release profile. The results showed that the physicochemical properties of the prepared nanoparticles are effectively controlled by the amount of shear stress transferred from the energy source to the emulsion, which is strongly correlated to the ultrasonication time.
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Design of controlled release non-erodible polymeric matrix tablet using microwave oven-assisted sintering technique
p. 176
DM Patel, BK Patel, HA Patel, CN Patel
DOI
:10.4103/0975-1483.83755
The objective of the present study was to evaluate the effect of sintering condition on matrix formation and subsequent drug release from polymer matrix tablet for controlled release. The present study highlights the use of a microwave oven for the sintering process in order to achieve more uniform heat distribution with reduction in time required for sintering. We could achieve effective sintering within 8 min which is very less compared to conventional hot air oven sintering. The tablets containing the drug (propranolol hydrochloride) and sintering polymer (eudragit S-100) were prepared and kept in a microwave oven at 540 watt, 720 watt and 900 watt power for different time periods for sintering. The sintered tablets were evaluated for various tablet characteristics including dissolution study. Tablets sintered at 900 watt power for 8 min gave better dissolution profile compared to others. We conclude that microwave oven sintering is better than conventional hot air oven sintering process in preparation of controlled release tablets.
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Dissofilm: A novel approach for delivery of phenobarbital; design and characterization
p. 181
SK Yellanki, S Jagtap, R Masareddy
DOI
:10.4103/0975-1483.83756
An attempt to develop and evaluate mouth-dissolving film of phenobarbital for quick effect in treatment of epilepsy occurring in pediatric population has been made in the present study. Suitable film formers and plasticizers are selected based on optimization studies. Effect of superdisintegrants in formulation of mouth dissolving films at different concentrations has been investigated. Films were prepared by solvent casting method. The prepared films were evaluated for physicochemical parameters,
in vitro
disintegration and dissolution time,
in vitro
release rate study, stability study, and
in vivo
animal safety study. The best formulation was found to be F3 showing 96.57% drug release in 14 min, following first-order kinetics. X-Ray diffraction studies show change in crystalline nature of drug in formulation.
In vivo
studies in hamster reports effective and safe use of formulation in animals.
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Preparation and evaluation of mixture of eudragit and ethylcellulose microparticles loaded with ranolazine for controlled release
p. 189
DV Gowda, MP Gowrav, HV Gangadharappa, MS Khan
To minimize the unwanted toxic effects of anti-anginal ranolazine by kinetic control of drug release, it was entrapped into gastro-resistant, biodegradable eudragit (EU) and ethyl cellulose (EC) binary blend using phase separation method. Ten formulations were prepared using different polymer blend ratios and solvent. The prepared microparticles were characterized for micromeritic properties, polymer drug compatibility by Fourier Transform Infrared Spectroscopy (FT-IR) and Differential Scannibg Calorimetry (DSC), and surface morphology by Scanning Electron Micrography (SEM). The yield of microparticles was up to 90% and more than 98% of the isolated microparticles are having volume mean diameter of 285 μm. The obtained angle of repose, percentage Carr's index and tapped density values were within the limits indicating good flow properties. The surface morphology revealed that particles were free-flowing, spherical, with minute pores and invert dents on the surface. The prepared microparticles were evaluated for percentage yield, encapsulation efficiency and
in vitro
release studies. FT-IR and DSC studies showed no chemical interaction between the drug and used polymers The
in vitro
drug release studies were carried out using pH 1.2 acid buffer and pH 7.4 phosphate buffer. EU acts as an excellent pH-dependent binder and helps to release the drug in the intestine. The drug release kinetics followed different transport mechanisms. Increasing the weight fractions of EU and decreased EC helps to control the drug release from the particles. From the differential (
f
1
) and similarity factor (
f
2
), Formulation F5 was the formulation most similar to the commercially available oral formulation as reference standard. The drug release performance was greatly affected by the materials used in microparticle preparations, which allow absorption in the intestinal tract.
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Preparation and characterization of metformin hydrochloride - compritol 888 ATO solid dispersion
p. 197
SC Jagdale, SA Patil, BS Kuchekar, AR Chabukswar
DOI
:10.4103/0975-1483.83758
Metformin hydrochloride (MET) sustained-release solid dispersions (SD) were prepared by the solvent evaporation and closed melt method, using compritol 888 ATO as the polymer with five different drug-carrier ratios. Characterization of solid dispersion was carried out by Fourier Transform Infrared (FTIR) spectroscopy, ultraviolet (UV) spectroscopy, Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD). The FTIR and UV studies suggested that no bond formation had occurred between the polymer and the drug. DSC and XPRD results ruled out any interaction or complex formation between the drug and the polymer. The formulated SD had acceptable physicochemical characters and SD with a 1 : 4 drug : Polymer ratio, which released the drug over an extended period of eight-to-ten hours. The data obtained from the
in vitro
release studies were fitted with various kinetic models and were found to follow the Korsmeyer-Peppas equation. The prepared SD showed good stability over the studied time period. The solvent evaporation method was found to be more helpful than the closed melt method, giving the sustained release action. The SD with a 1 : 4 ratio of drug to polymer, by the solvent evaporation method, was selected as the most effective candidate for the subsequent development of a well-timed, sustained-release dosage form of the drug.
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Preparation and evaluation of silymarin
β
-cyclodextrin molecular inclusion complexes
p. 205
A Ghosh, S Biswas, T Ghosh
DOI
:10.4103/0975-1483.83759
Silymarin is a hepatoprotective agent, having poor water solubility and oral absorption of about 23 - 47%, leading to low bioavailability of the drug. The aim of the present study is to improve the solubility and dissolution rate and in turn the hepatoprotective activity of the drug, by formulating its inclusion complex with beta (β)-cyclodextrin, using different methods. The phase solubility analysis indicates the formation of 1:1 molar inclusion complex of the drug with beta cyclodextrin. Apparent stability constant for Silymarin (K
c
) was 722 K
−1
with β-cyclodextrin complex. The inclusion complexes were prepared by four different methods, namely, physical mixing, kneading, co-precipitation, and solvent evaporation. The prepared complexes were characterized using differential scanning colorimetry, scanning electron microscopy, and x-ray diffractometry. The inclusion complex prepared by the co-precipitation methods exhibits an overall best result, with respect to the formulation of sustained release formulations.
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Hordeum vulgare
hull in the design of fast disintegrating tablets
p. 211
H Rajpurohit, P Sharma, S Sharma, S Purohit, A Bhandari
DOI
:10.4103/0975-1483.83763
In the present study, fast disintegrating tablets were designed with a view to enhance patient compliance. In this method, the hull of
Hordeum vulgare
, cross carmellose sodium, and sodium starch glycolate were used as superdisintegrants (4 and 6%), along with microcrystalline cellulose and mannitol, to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water absorption ratio and
in vitro
dispersion time. Based on the
in vitro
dispersion time, the formulations were tested for the
in vitro
drug release pattern. Tablets having
H. vulgare
hull showed the release profile comparable to those tablets having sodium starch glycolate and cross carmellose sodium.
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Formulation and evaluation of solid lipid nanoparticles of ramipril
p. 216
P Ekambaram, A Abdul Hasan Sathali
DOI
:10.4103/0975-1483.83765
Solid lipid nanoparticles are typically spherical with an average diameter between 1 and 1000 nm. It is an alternative carrier system to tradition colloidal carriers, such as, emulsions, liposomes, and polymeric micro and nanoparticles. Ramipril is an antihypertensive agent used in the treatment of hypertension. Its oral bioavailability is 28% and it is rapidly excreted through the renal route. This drug has many side effects such as, postural hypotension, hyperkalemia, and angioedema, when given as an immediate dosage form. To overcome the side effects and to increase the bioavailability of ramipril, solid lipid nanoparticles of ramipril are prepared by using lipids (glyceryl monostearate and glyceryl monooleate) with stabilizers (tween 80, poloxamer 188, and span 20). The prepared formulations have been evaluated for entrapment efficiency, drug content,
in-vitro
drug release, particle size analysis, scanning electron spectroscopy, Fourier transform-infrared studies, and stability. A formulation containing glyceryl monooleate, stabilized with span 20 as surfactant showed prolonged drug release, smaller particle size, and narrow particle size distribution, as compared to other formulations with different surfactants and lipids.
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PHARMACOGNOSY
Pharmacognostic standardization, physico- and phytochemical evaluation of
Amaranthus spinosus
Linn. root
p. 221
D Jhade, D Ahirwar, R Jain, NK Sharma, S Gupta
DOI
:10.4103/0975-1483.83770
Amaranthus spinosus Linn.
(Amaranthaceae) is found throughout India. This tree species has been of interest to researchers because it is a medicinal plant employed in the Indian traditional system of medicine. Pharmacognostic standardization; physico-and phytochemical evaluation of the roots of
Amaranthus spinosus
was carried out, to determine its macro-and microscopical characters, and also some of its quantitative standards. Microscopical studies were done by using the trinocular microscope. Total ash, water-soluble ash, acid-insoluble ash, sulfated ash values, and alcohol-and water-soluble extractive values were determined for physico-chemical evaluations. A preliminary phytochemical screening was also done to detect different phytoconstituents. Microscopically, the root showed cork, cortex, stellar region, and calcium oxalate crystals. Powder microscopy showed anamalous secondary growth in between the xylem vessels and Calcium Oxalate crystals in the cortex region. Total ash was approximately three times more than acid insoluble and water soluble ash. The ethanol soluble extractive was approximately the same as the water soluble extractive. Thin Layer Chromatography (TLC) of the Petroleum-ether extract using Benzene : Ethyl acetate (6 : 1), showed six spots. In the chloroform extract, using Benzene : Ethyl acetate (4 : 1) nine spots were seen, and in the ethanol extract, using Chloroform: Methanol (93 : 7), only four spots were observed, using Iodine vapor as a viewing medium. Phytochemically, the root exhibited terpenes, alkaloids, glycosides, and sugars. These findings might be useful to supplement information with regard to its identification parameters, which are assumed significant in the way of acceptability of herbal drugs, in the present scenario, which lacks regulatory laws to control the quality of herbal drugs.
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Sepbox technique in natural products
p. 226
M Bhandari, Anil Bhandari, A Bhandari
DOI
:10.4103/0975-1483.83771
Natural compounds still play an increasingly important role in many areas of research and development. Their structural diversity is enhanced by the synthetic potential of combinatorial chemistry. Fractionation and separation of samples obtained from nature remain time-consuming, tedious and extremely expensive even though the assays for testing these samples have become faster and more cost-effective thanks to advanced high-throughput screening (HTS) processes. Today, sepbox is the standard technology used for separating compounds from natural resources. Fractionations and separation of samples obtained from nature remain very difficult. Automation of sample preparation therefore has great economic potential. The unique sepbox concept allows processing sample automatically and will make up to 30 times faster than by using a conventional process.
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PHARMACOLOGY
Central nervous system effects of Iso-6-spectaline isolated from senna spectabilis var. excelsa (schrad) in mice
p. 232
FO Silva, MGV Silva, GS Cerqueira, EB Sabino, AAC Almeida, JP Costa, RM Freitas
DOI
:10.4103/0975-1483.83772
The central nervous system (CNS) depressant and anticonvulsant activities of iso-6-spectaline (SPEC) were investigated in animal models. The SPEC from
Senna spectabilis
var
. excelsa
(Schrad) (0.1, 0.5 and 1.0 mg/ kg) injected by oral route (p.o.) in mice caused a significant decrease in the motor activity up to 30 days after the administration and in the dose of 1.0 mg/kg significantly reduced the remaining time on the Rota-rod apparatus. Additionally, SPEC (0.1, 0.5 and 1.0 mg/kg, p.o.) was also capable of promoting increase of latency for development of convulsions induced by pentylenetetrazole. This SPEC was also capable of promoting an increase of latency for development of convulsions induced by picrotoxin at highest dose. In the same way, the anticonvulsant effect of SPEC was affected by pretreatment with flumazenil, a selective antagonist of the benzodiazepine site of the GABA
A
receptor. These results suggest possible CNS depressant and anticonvulsant activities in mice that needs further investigation.
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Aqueous methanol extracts of
Cochlospermum tinctorium
(A. Rich) possess analgesic and anti-inflammatory activities
p. 237
TS Ahmed, MG Magaji, AH Yaro, AM Musa, AK Adamu
DOI
:10.4103/0975-1483.83774
Cochlopermum tinctorium
A. Rich. (Cochlospermaceae) is a commonly used medicinal plant in the West Africa sub-region for the management of various conditions including pain and inflammatory conditions. In the present study, we report the analgesic and anti-inflammatory activities of the aqueous methanol leaf (20-80 mg/kg), root (7.5-30 mg/kg), and root bark (20-80 mg/kg) extracts of the plant. The analgesic potentials of the extracts were studied using acetic acid induced writhing and hot plate tests in mice while the anti-inflammatory activity was investigated using carrageenan-induced paw edema in rats.The extracts significantly and dose dependently inhibited the acetic acid-induced writhing in mice. However, the highest protection against writhing was produced by aqueous methanol leaf extract at the dose of 80 mg/kg (96.65%) which even was greater than that of the standard agent, ketoprofen (82.30%). The extracts did not significantly increase mean latency of response in the hot plate test. However, aqueous methanol root bark extract at the dose of 20 mg/kg significantly (
P
< 0.05) increased the mean latency of pain response. While the extracts of the root and root bark extracts of the plant afforded non dose-dependent protection against carrageenan-induced edema, the aqueous methanol leaf extract significantly and dose-dependently inhibited carrageenan-induced hind paw edema at the end of the third hour.The present study suggests that the aqueous methanol leaf, root, and root bark extracts of
Cochlopermum tinctorium
possess analgesic and anti-inflammatory activities which lend some credence to the ethnomedical claim of the use of the plant in the management of pain and inflammatory conditions.
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PHARMACEUTICAL CHEMISTRY
Studies on the anthelmintic property of aminobenzylated mannich bases
p. 243
KC Chaluvaraju, KI Bhat
DOI
:10.4103/0975-1483.83775
Studies were conducted on the anthelmintic property of about 15(e-h, 1e-1h, 2d-2f and 3e-3h) synthesized aminobenzylated Mannich bases bearing N-methyl piperazine using Indian earthworms
Pheritima Posthuma
against piperazine citrate as standard reference. Three concentrations of each compound (0.1, 0.2, 0.3% w/v) were studied, which involved the determination of paralysis and death time of the worms. The compound 1g exhibited the most significant anthelmintic activity among all the compounds screened against the worms as compared to standard drug.
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In-silico comparative study and quantitative structure-activity relationship analysis of some structural and physiochemical descriptors of elvitegravir analogs
p. 246
R Satpathy, S Ghosh
DOI
:10.4103/0975-1483.83776
Elvitegravir is a new-generation drug which acts as an integrase inhibitor of the HIV virus. The potential inhibition has been tested from the clinical trial data. Here the work basically deals with the quantitative structure-activity relationship (QSAR) analysis by considering some of the physiochemical descriptors like molecular weight, logP, molar volume, and structural descriptors like Winers index, and molecular topological index of the drug analogs. The descriptors were calculated from the E-Dragon server and the multiple linear regression equation models were built by using Minitab tools. The different combinations of structural and physiochemical descriptors were considered for model derivation. The best three models were chosen by observing high R-Sq value, high F-value and low residual errors. The
P
values (regression) for the three models indicates the significance of the considered descriptors.The overall results obtained with these model suggest that for this perticular drug the activity is dependent on physiochemical descriptors.
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PHARMACY PRACTICE
Patient-physician communication barrier: A pilot study evaluating patient experiences
p. 250
TM Khan, MA Hassali, MSM Al-Haddad
DOI
:10.4103/0975-1483.83778
This study aims to identify the patient-physician communication barriers in the primary healthcare setting in Pulau Penang, Malaysia. A cross-sectional study was designed to attain the objectives of the study. A self-developed 17-item study tool was used to explore respondent's perception about the barriers they have faced while communicating with physician. The reliability scale was applied and internal consistency of the study tool was estimated on the basis of Cronbach's alpha (α = 0.58). The data analysis was conducted using statistical package for social sciences students SPSS 13
®
.
Chi Square
test was used to test the difference between proportions. A total of
n
= 69 patients responded to this survey. A higher participation was seen by the male respondents, 39 (56.5%). About 52 (76.5%) of the respondents were satisfied with the information provided by the physician. In an effort to identify the patient-physician barriers, a poor understanding among the patients and physician was revealed. 16 (23.5%) respondents disclosed lack of satisfaction from the information provided to them. Overall, it is seen that lack of physician-patient understanding was the main reason that result hindrance in the affective communication. Moreover, there is a possibility that a low level of health literacy among the patients and inability of the physician to affectively listen to patients may be the other factors that result in a deficient communication.
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GENERAL PHARMACY
Pharmacovigilance of herbal products in India
p. 256
P Wal, A Wal, S Gupta, G Sharma, AK Rai
DOI
:10.4103/0975-1483.83780
Herbal formulations being widely accepted therapeutic agents as antidiabetics, antiarthritics, hepatoprotectives, cough remedies, memory enhancers, and adaptogens. The commonest myth regarding herbal medicines is that these medicines are completely safe, and can therefore be safely consumed by the patient on his/her own, without a physician's prescription. This belief has led to large-scale self-medication by people all over the world, often leading to disappointing end-results, side-effects, or unwanted after-effects. There is an increasing awareness at several levels of the need to develop pharmacovigilance practices for herbal medicines. The current model of pharmacovigilance and its associated tools have been developed in relation to synthetic drugs, and applying these methods to monitoring the safety of herbal medicines presents unique challenges in addition to those described for conventional medicines. Several problems relate to the ways in which herbal medicines are named, perceived, sourced, and utilized. This may be because of differences in the use of nonorthodox drugs (e.g., herbal remedies) which may pose special toxicological problems, when used alone or in combination with other drugs. The purpose of pharmacovigilance is to detect, assess, and understand, and to prevent the adverse effects or any other possible drug-related problems, related to herbal, traditional, and complementary medicines.
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