Journal of Pharmaceutical and Medicinal Chemistry

 Assessment of chocolate toxicity is often carried out by veterinarians in pet clinics. The more reliable method used for this assessment is described here. The calculations involved in the assessment are complex, confusing, time consuming and not easily reproducible. Spreadsheet is a computer application in which data are arranged in rows and columns of a grid and can be manipulated and used in calculations. In today’s era of smart phones, tablet PCs and netbooks, where a spreadsheet program in the form of Microsoft Excel [1] is readily accessible by most veterinarians, it should be possible to adapt the various laborious steps involved in the said method to a spreadsheet program by writing simple logical codes in the spreadsheets to do the calculations in a simple, clear, faster, reproducible, accurate and user friendly manner. This article describes a spreadsheet program (CHACToxi Calc) to calculate the chocolate toxicity.

Keywords: Chocolate Toxicity Calculator; Chocolate Toxicity in Dogs; Toxicity Meter; Caffeine Poison in Dogs.

 Oxazolones or oxazolidinone or azlactones are five membered heterocyclic lactams derived from oxazole, also known as (4H)-oxazol 5-ones. Oxazolones have been very widely explored as important synthons for the synthesis of several biologically active molecules. Oxazolones derivatives have been used as starting materials for the synthesis of modified á- amino acids, peptides, other heterocycles, and biosensors. This review preesnts the various methods of synthesis of oxazolone derivatives.

Keywords: Oxazolone; Hippuric Acid; Benzoylglycine.

 Patent is an exclusive right granted for 20 years in exchange of complete discloser of the innovation. Different countries have their different patent laws. The main objective is comparatively evaluation of the patent term extensions granted in developed countries like US, Europe, etc and developing countries like India. Study the strategies used by these countries for extending the patent term. Study of patent laws and their amendments, different cases and conditions and thus analyse the facts and understand eligible conditions in which an extension can be granted. Extension of a patent term is to compensate the regulatory delay which occurs during the approval process of marketing authorisation for the patent, due to which the patentee is unable to enjoy the monopoly. Thus patent term extension encourages innovators to invest in the researches and bring out innovations. Here comparitive evaluation of patent term extension between developed and developing countries is discussed and all pros and cones are evaluated which would be helpful in drafting the policies of patent term extension for countries like India.

Keywords: Patent; Patent Term Adjustment; Patent Term Extension; Supplementary Protection Certificate.

 The development of bioanalytical method is of paramount importance during the pre-clinical and clinical stage of drug development. Analytical method development where the appropriate bioanalytical method with its various parameters is developed and the assay is defined and application of the bioanalytical to actual analysis of sample from bioavailability, bioequivalence and pharmacokinetic studies. Bioanalytical methods are used for the quantitative analysis of drugs and their metabolites in the biological matrices like saliva, plasma, blood, serum, urine. In method development sample preparation and sample analysis are two important part. For sample analysis generally chromatographic technique are used like (HPLC, LC-MS/MS, GC, UPLC). After method development validation of that bioanalytical method is important. Method validation is a process that demonstrates that a method will successfully meet or exceed the minimum standard recommended in the USFDA or other guideline for accuracy, precision, selectivity, sensitivity, reproducibility and stability. 

Keywords: Bioanalytical Method Development; LC-MS/MS; Bioanalytical Method Validation.

 A specific, accurate, precise and reproducible RP HPLC method has been developed and subsequently validated for the simultaneous estimation of Ilaprazole and Domperidone in pharmaceutical dosage form. The proposed HPLC method utilizes hypersil (Thermo scientific) C18 column (250 mm × 4.6 mm id, 5 ìm particle size), and mobile phase consisting of water: Acetonitrile: Acetic acid (30:70:0.1) at a flow rate of 1.0 mL/ min. Quantitation was achieved with PDA detection at 255 nm based on peak area with linear calibration curves at concentration ranges 5-15 g/ ml for Ilaprazole and 15-45 g/ml for Domperidone. The retention time of Ilaprazole and Domperidone were found to be 3.753 min and 6.120 min respectively. The stability studies were carried out and method was validated in terms of accuracy, precision, linearity, limits of detection, limits of quantitation and robustness. This method has been successively applied to marketed formulation and no interference from the formulation excipients was found. 

Keywords: Ilaprazole; Domperidone; Stability Indicating Assay; HPLC.

 Oral route is the most common and preferred route for the drug administration due to convenience and ease of administration. Technology Catalysts International reported in 2002 that approximately 35-40% of all new chemical compounds suffer from poor aqueous solubility. Therefore, enhancing drug dissolution became one of the major challenges for pharmaceutical scientists over the past decade. Lipid formulations and in particular SMEDDS/ SNEDDS Self- icro emulsifying Drug Delivery Systems can induce a considerable increase in dissolution rate Class II-IV drugs are considered the best candidates for intervention by formulation e.g. in self- mulsifying dosage forms. Aim: Cefdinir is a poorly water-soluble drug with varying bioavailability. The main purpose of present work was to develop self-micro emulsifying drug delivery system (SMEDDS) for enhancing solubility and bioavailability of Cefdinir is indicated for the treatment of bronchitis as well as for the treatment ofear, nose, throatdisorder. Materials and Method: Cefdinir had highest solubility in labrafac with comparison to other lipid vehicles. Emulsification study results were shown that tween 20 has highest solubility capacity of oil was higher (0.8528 ± 0.4075mL) than other surfactant.Sotween 20 was selected as surfactant. From the result were shown that PEG 400 has highest solubility capacity of oil (2.65 ± 1.801 mL). So PEG 400 was selected as cosurfactant. The formulation of Cefdinir SMEDDS was optimized by a simplex lattice design. The optimal formulation of SMEDDS was comprised of 20% oil (Labrafac), 60% surfactant (Tween-80) and 20% co-surfactant (PEG-400). Results and Discussion: Pseudo-ternary phase diagrams were constructed to identify the efficient selfemulsification region. Optimal ratio of surfactant to co-surfactant was selected to be 4:1. A suitable SMEDDS formulation should have a minimum self emulsification time, maximum% Transmittance, maximum time require to 20% of drug release.The individual desirability for each response was calculated and batch F2 showed the highest overall desirability therefore this batch considered to be the best batch. In order to obtain both high %Transmittance and high Cumulative %release, the appropriate ratio of components was chosen for optimized formulation, which consisting of oil (20%), surfactant (60%), co-surfactant (20%).The average globule size of SMEDDS containing Cefdinir was about 87.60 nm when diluted in water. No significant variations in globule size and In vitro diffusion studies showed remarkable increase in dissolution of drug. Order of drug release was F-2> F-4> F-1 > F-7> F-3>F-6 > F-5.  Conclusion: The data suggest use of SMEDDS to provide great potential as an alternative to traditional oral formulations of Cefdinir. 

Keywords: Cefdinir; Self-Micro Emulsifying Drug Delivery System (SMEDDS); Simplex lattice Design; Globule Size.

 Background and Objective: The polyherbal formulation (PHF) consisted of Piper betel leaves and Acacia catechu. The leaves of Piper betel has major active constituents as Hydroxychavicol and eugenol which are readily extracted by water. The bark of Acacia catechu mainly contains catechin, and epicatechin. The extract of Piper betel have been tested for Antiplatelet activity against various pro aggregating substances, like PAF, TXB2, PGD2, and ADP, collagen and arachidonic acid. Anti-cancer activity was evaluated by MTT (tetrazolium) assay using human breast cancer cell line (MCF-7). Anti-arthritic activity of Hydroxychavicol was evaluated at graded doses which significantly decreased the expression of IL-1, PGE2, LTB4, and nitric oxide levels. Antioxidant and anti-inflammatory activities of Hydroxychavicol was assessed using hyaluronidase (HYA), xanthine oxidase (XOD) and lipoxygenase (LOX) inhibition assays. The extracts of Piper betel and Acacia catechu also exhibited significant inhibition in XOD and LOX assays. Antimutagenic activity was exhibited by dose dependent suppression of dimethylbenzanthracene induced mutagenesis in S. typhimurium strain TA98 with metabolic activation and also showed that Hydroxychavicol was more potent than eugenol in this respect. The anticoagulant activity of the compound was assayed by the activated partial thromboplastin time (APTT), prothrombin time (PT), and these assays were compared with the anticoagulant heparin which showed that it acted on the intrinsic as well as extrinsic pathways of the blood coagulation systems. It could be a potential therapeutic agent for prevention and treatment of Atherosclerosis and other cardiovascular diseases. Literature search reveals the traditional use of Piper betel leaves as an aromatic, stimulant, carminative, astringent and antiseptic (Kirtikar and Basu, 1987 and Panda, 2004). The Acacia catechu has antiviral, anti-inflammatory, hepatoprotective and spasmolytic (Dahanukar et al, 2000). To confirm the traditional claim of antiulcer activity of Piper betel leaves and Acacia catechu scientifically, the study was undertaken to investigate the antiulcer and antisecretory activity of Poly Herbal Formulation (PHF) consisting of Piper betel leaves and Acacia catechu in experimentally induced gastric ulcer models in rats. The study supported that PHF has anti-ulcerogenic activity as it decreased ulcer index, volume of gastric acid secretion, total acidity, total acid output, pepsin output, TC/PR ratio, protein content and MDA content while increasing total carbohydrates as compared to disease control group. Thus, the antisecretory and cytoprotective activity of PHF are confirmed and further studies are warranted to investigate the efficacy of the same. Methods: Wistar albino rats of either sex were treated with PHF in dose of 100mg/kg and 200mg/kg for 7 days p.o. once a day in Aspirin + pylorus ligation induced gastric ulcer model and 200mg/kg in ethanol induced gastric ulcer model in rats. The physical parameters, acid secretory parameters, dissolved mucosubstances and MDA content were analyzed. Results and Discussion: When compared to disease control group, PHF treated group showed significant decrease in ulcer index (p<0.001), Volume of gastric acid secretion (p<0.01), Total Acidity (p<0.01), Total Acid Output (p<0.01), Pepsin output (p<0.01) and Protein content (p<0.01) while significant increase in Total carbohydrates (p<0.01) and total carbohydrate: Protein (TC:PR) ratio (p<0.01) in Aspirin + Pylorus ligation induced gastric ulcer model. Significant decrease in ulcer index (p<0.01) and MDA content (p<0.001) was seen in ethanol induced gastric ulcer model in rats. onclusion: The present study demonstrated that PHF possess significant antiulcer activity against experimentally induced gastric ulcer in rats which might be attributed to its antioxidant activity of major phytochemical constituent Hydroxychavicol and catechin. 

Keywords: Hydroxychavicol; Catechin; Acacia Catechu; Piper Betel Leaves; Anti Ulceractivity. 

 A simple, novel, rapid, precise, accurate, specific and cost effective High performance thin layer chromatographic method has been developed and validated for Simultaneous Estimation of Nifedipine and Lidocaine in Cream Dosage Form. The Stationary Phase used was C18Hypersil BDS column and the Mobile Phase used was Mixture of Buffer (pH 3.0): Methanol (50:50). The Developed Method was Validated As per International Conference on Harmonization (ICH) guidelines. Calibration Curve was found to be Linear and the Correlation Coefficient was found to be 0.998 and 0.999 for Nifedipine and Lidocaine respectively. The Limit of Detection for Nifedipine and Lidocaine was found to be 0.18µg/ml and 0.59µg/ml respectively. The Limit of Quantization for Nifedipine and Lidocaine was found to be 0.55µg/ml and 1.79µg/ml respectively. The Degradation Study Preformed are Oxidative, Acidic, Basic, Thermal and Photolytic. 

Keywords: Validation; HPLC; Nifedipine; Lidocaine; Cream Dosage Form.

Insulinresistance has been considered as the most important component of type 2 diabetes mellitus (DM2). Plants used infolkmedicine to treat diabetes mellitusre present aviable alternative forthe control ofthis disease. This study was aimed to examine the antidiabetic effects of dichlorome thane extract of Caesalpinia bonducella in an animal model of DM2. Diabetes was induced in male Wistarrats (6-8 week sold) by feeding 21% fructose in drinking water for 8 weeks. They were treated with dichlorome thane extract of leaves of Caesalpinia bonducella (DCM 200, DCM 400) for 2 weeks. After diabetes induction and the last day of the experiment, body weight, fasting blood glucose, plasmainsulin, urinevolume and urine glucose were assayed. Blood glucose, plasmainsulin, urine gluco sean durin evolume were in creased significantly after 8 weeks of high fructose feeding (P<0.005); DCM 200 reduced body weight, plasma insulin andurineglucose (p<0.05)and no significant difference in blood glucose and urine volue. While DCM 400 significantly decreasedblood glucose (p<0.05), urineglucose (p<0.01) and plasma insulin (p<0.01), body weight (p<0.05)andurine volume (p<0.05) when compared with that of 8th week values. The study showed hypoglycemia effects and improvement of insulin resistance of dichloromethane extract of leaves of Caeslpinia bonducella. These result scan bee xtra polated to human sand these extracts might be useful in the treatment of insulin resistance. 

Keywords: Hypoglycemia; Insulin Resistance; Fructose; Caesalpenia bonducella.

 In the present study we selected a plant namely allophylus serratus belonging to the family (sapindaceae) commonly known as Triputa (in Sanskrit). It is a large shrub or small tree grows up to 10 meters in height. It contains beta-sitosterol, phenacetamide, two flavonoid glycosides like luteolin-7-o-[beta]-D-glucopyranoside and apigenin- 4’-o[beta]-D-glucoside, quercetin, pinitol, rutin etc. It is useful in bone fractures, dislocations, Inflammations, ulcers, wounds, dyspepsia, anorexia and diarrhoea. The fruits are sweet cooling and nourishing tonic. Roots of widely grown plant Allophylus serratus reported to possess a very high amount of polyphenols and gallic acid which are well known potent antioxidants. Evaluation of the hepatoprotective activity was done by estimating the biochemical marker like SGPT, SGOT, ALP, LDH, total bilirubin, total protein in serum. EEAS significantly reversed the above parameters to near normal levels and the activity of EEAS was comparable to that of standard silymarin. The present studies indicated that the EEAS possess potent hepatoprotective activity comparable to standard LIV 52. The possible hepatoprotective mechanism of roots of llophylus serratus may be via its antioxidant property. 

Keywords: EEAS; Hepatotoxins; CCl 4, Histopathology.

 Bioanalytical method development plays importance role in the preclinical and clinical studies. Pharmacokinetics of any drug and/or its metabolite can be recognised by bioanalytical studies. The quantitative analysis of drugs and their metabolites in the biological media is done by bioanalytical studies. Physico-chemical and biological techniques are used for these studies. Each bioanalytical method should be selective, sensitive and reliable for the quantitative evaluation in drug discovery process. Bioanalytical method development consists of sample preparation, chromatographic separation and detection by using proper analytical method. Each developed method should be validated as per the regulatory authorities, so as to give reliable and reproducible method for the intended use. Many analytical techniques can be use for bioanlysis, LCMS/MS is one of them. In Liquid chromatographymass spectrometry (LC- S/MS) the separation of analyte is done by LC and detection is carried out by MS. LC-MS/MS prominently used in evaluation and interpretation of bioavailability, bioequivalence and pharmacokinetic data. This review also focused on various validation parameters such as: accuracy, precision, sensitivity, selectivity, standard curve, limits of quantification, range, recovery stability, etc.

Keywords: Bioanalytical; Liquid Chromatography; Spectrometry; Bioanalysis; Validation.

 This work is concerned with application of simple, accurate, precise and highly selective reverse phase high performance liquid chromatographic (RP-HPLC) method for simultaneous estimation of duloxetine hydrochloride (DUL)and methylcobalamin (MCB) in combined dosage form. chromatographi separation was achieved by using a reverse phase C18 coloum (Hypersil BDS 250X 4.6X5µm). The mobile phase composed methanol : phosphate buffer in ratio 70:30 at flow rate of 1ml/min .The ph was adjusted to 4.5 with .1N NaOH. Detection was carried out using a UV-vis detector at 215 nm. The mean retention time of duloxetine hydrochloride (DUL)and methylcobalamin(MCB) was found to be 3.3 min 6.7 min respectively. The method was found to be linear in the range of 30 - 90 µg/ml and 2.5-6.75 µg/ml for DUL and MCB respectively, with mean recovery of 98.88 % DUL and 100.22% for MCB the correlation coefficient for both DUL and MCB were closed to one. The developed method was validated according to ICH guidelines and values of accuracy, precision and other statistical analysis were found to be in good accordance with the prescribe values thus proposed method was successfully applied for simultaneous determination of DUL and MCB in routine analysis of formulation.