Indian Journal of Pharmacy and Pharmacology

81-84

Authors: Bornali Dutta, Prasanta Kr. Bhattacharya, Mangala Lahkar

Aim: To explore the association of CYP2C9 genetic polymorphism in Type2 diabetic patient under the treatment of sulfonylurea (glimepiride) and undergoing adverse drug reactions (ADRs) Glimepiride, a sulfonylurea hypoglycemic agent, is metabolized by cytochrome P450 2C9 (CYP2C9) which is known to have genetic polymorphisms. The most frequent polymorphism is the single nucleotide polymorphism (SNP) which describes the occurrence of at least 2 different alleles for one gene differing only at one specific DNA position Studies shows that CYP2C91*,CYP2C9*2 and CYP2C9*3 are the most important known alleles of CYP2C9. The wild type allele CYP2C91* is with normal enzyme activity CYP2C92*allele has a nucleoside change from cytosine to thiamine at gene position 3608 and hence causes a substitution of arginine by cysteine at protein position144; it has only minor effect on substrate affinity. In CYP2C93* allele nucleoside change from adenine to cytosine at gene position 42614 , results in an amino acid substitution of isoleucine by leucine at protein position 359 this substitution results in a loss up to 70 % of the enzyme activity with CYP2C93* allele as compared with the wild type allele CYP2C91* Patient possessing a decreased enzyme activity because of its genetic disposition, will have a higher bioavailability and smaller clearance for drugs metabolized via this specific CYP. Impaired metabolism of sulfonylurea due to gene polymorphism in the metabolic enzyme CYP2C9 might lead to adverse drug reaction like hypoglycaemia, so genotyping of CYP2C9 may thus serve as a useful tool for predicting adverse effects caused by sulfonylurea and thus helps the clinicians for safer prescribing of oral hypoglycaemic agents. Material And Methods: Type2 diabetic patients of Guwahati Medical College Hospital, Assam under the treatment of sulfonylurea (glimepiride) was identified.70 patients with glimepiride treatment at a dose of 2mg once daily and undergoing therapy from day 1(one) to 2 years were possible to be identified in this 2 years of the study.32 patients had no complain for the drug but 38 patients suspected of having at least one adverse drug reaction(ADR) . Blood samples of patients experiencing ADRs as well as from patient without any complain for the drug were collected after written informed consent and prior ethical committee clearance ,reference no.MC/190/2007/Pt11/22 date:30/03/11.DNA was isolated , alleles CYP2C91*(wild type) and CYP2C92*, CYP2C93* variant form was detected by Polymerase chain reaction –Restriction fragment length polymorphism. Results: Variant form CYP2C92*and CYP2C93* allele on both groups with and without ADR experienced during the course of therapy was studied along with the wild type CYP2C91* from the variant form. Allele CYP2C9 1*(wild type, having 80% enzyme activity) predominates in the group experiencing no any adverse drug reaction. No variant form CYP2C92* allele was able to be identified in any of the two groups whereas variant form CYP2C93* allele was identified in few samples of the group with ADRs. A test for significance (chi square test) for occurrence of allele in parameter like adverse drug reaction was done. The p value (<0.05) obtained was found to be statistically significant.

90-99

Authors: G. Vidyasagar, Srinivasulu C

The stability of pharmaceutical products plays an important role from the economic point of view. There are not many studies that report about the stability of drugs past their expiration dates. The objective of the current study was to determine the tablet content of expired tablets of Frovatriptan where expiry date has not exceeded and to develop simple, accurate, sensitive and stability indicating RP-HPLC method for the determination of per cent drug remained of Frovatriptan in the presence of its degradation products in bulk drug, expired tablets and tablets whose expiry date has not been exceeded. Drug was subjected to all stress conditions such as hydrolysis (acidic and alkaline), oxidation, photolysis, thermal degradation and humidity study. Content determination was performed using RP-HPLC method; the percent of dissolved substance from tablets was also performed. All stressed samples were successfully analyzed on C18 column using mobile phase acetonitrile: methanol: 0.1% orthophosphoric acid 45:15:40 (v/v/v) mobile phase (pH5.6). A flow rate was maintained at 1 Ml/min and detection was made at 245 nm. The proposed method was validated with regard to linearity, sensitivity and accuracy and precision. No discrepancies between the results of determination and the declared values range for all the analyzed tablets were observed. The results of performed study might suggest that storage of analyzed batches of tablets over time period exceeding the expiry date given by the manufacturer did not influence their contents.

105-112

Authors: Aniket, A. Kumari, P. Kumari, S. Saurabh, L. Khurana, K. S. Rathore

The bioavailability and absorption of water soluble phyto constituents is erratic due to poor solubility of these constituents in gastrointestinal tract. This can be overcome by a novel delivery system known as phytosome technology in which water soluble phyto constituents are allowed to react with phospholipids. For better and improved bioavailability, natural phyto constituents must have a good balance between hydrophilicity (helps in dissolution in gastro-intestinal fluids) and hydrophobicity (helps to cross lipid rich cell membranes). This is achieved through phytosome technology. Phospholipids have a dual solubility and acts as an emulsifier. Phytosome technology acts as a bridge between novel and conventional delivery systems. Many products are available in the market based on this phytosome technology which includes popular herbal extracts such as Ginkgo biloba, Silybum marianum, grape seed, olive oil flavonoids etc.

119-133

Authors: Abhishek Soni, Raju L.

The aim of this study was to prepare Fast disintegrating tablet containing Hydrochlorothiazide by using Natural disintegrants. The tablets were prepared using micro crystalline cellulose as diluent and aspartame as sweetening agent along with Natural super disintegrant. The superdisintegrant used in this study was Isapghula mucilage and Banana powder. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio and disintegration time (DT) and dissolution study. Different concentration of superdisintegrant was used in this formulation as 2%, 4%, 6%, 8%. From the results obtained, it can be concluded that the tablet formulation prepared with 8% with Isapghula mucilage ie. 8 mg showed fast and higher drug release (97.68%) during in vitro dissolution study. Also the hardness, friability, dissolution rate and assay of prepared tablets (batch F8) were found to be acceptable according to standard limits.

139-142

Authors: Preeti Tyagi, Maloy B Mandal, A.N. Gangopadhyay

Atresia is the congenital obstruction with complete occlusion of intestinal lumen and responsible for 95% of congenital intestinal obstructions. Colonic atresia is a rare form of intestinal atresia. Because of its rarity, limited literature is available on management and outcome of this entity. Although new operative techniques and better perioperative managements have led to an improvement, but delay in intestinal motility recovery and long term decreased motility remained common problems in postoperative period. Most of the surgeons excise the atretic part and only few centimeter of just adjacent pre-atretic part. Most of the dilated pre-atretic part is not excised usually and considered as normal but study on its exact functional status is not available. This study was done on pre-atretic part of freshly excised specimen of a case of colonic atresia in vitro to know the functionality of this part which may be helpful to decide that it should be preserve or excise. After clearing of fecal matter, 2-3 millimeter wide and 15-20 millimeter long longitudinal strip was prepared and mounted in organ bath filled with Krebs Ringer solution continuously bubbled with 100% oxygen. Spontaneous contractions were observed with the frequency of approximately 3 peaks/ hour and amplitude of 27.23 gram per gram wet tissue. There was no response by lowest dose of histamine (0.1 μM) while dose dependent increase in the contractile force by different cumulative concentrations of histamine (1, 10 & 100 μM) was observed. It can be concluded that pre-atretic part is normal up to some extent especially in respect to the pacemaker activity and histaminergic pathway so it should be preserved. However, detailed functional and histopathological study on more number of cases as well as on control specimens by using different agonists and their blockers are needed.