Improved in vitro and in vivo performance of carbamazepine enabled by using a succinic acid cocrystal in a stable suspension formulation

Currently cocrystals are considered as an established approach for making crystalline solids with overall improved physico-chemical properties. However, some otherwise well behaving cocrystals undergo rapid dissociation during dissolution, with ultimate conversion to parent drug and thus apparent loss of improved solubility. The polymeric carriers are long known to manipulate this conversion during dissolution to parent crystalline drug, which may hinder or accelerate the dissolution process if used in a dosage form. The goal of this study was to deliver in vivo a more soluble carbamazepine-succinic acid [CBZ-SUC] cocrystal in suspension formulation utilizing Hydroxypropyl methyl cellulose [HPMC-AS] as a crystallization inhibitor and Polyvinyl carpolactam-polyvinyl acetate-polyethylene glycol graft co-polymer® as solubilizer. The concentration of these polymers were systemically varied during in vitro dissolution studies, while selected formulations from dissolution studies were tested in vivo. Pharmacokinetic studies [PK] in rabbits demonstrated that formulation F-X [1% cocrystal, 1% HPMC-AS and 2% Polyvinyl carpolactam-polyvinyl acetate-polyethylene glycol graft co-polymer caused almost 6fold improvement in AUCo-72 as well as much higher C[MAX] of 4.73microg.mL[+1] to that of l.OTmicrog.mL[+1] of unformulated 'neat' cocrystal given orally. When reference formulation of CBZ [F5-X] with similar composition to F-X were given to rabbits, cocrystal formulation gave 1.37fold bioavailability than CBZ reference formulation. C[MAX] of reference formulation observed was 3.9microg.mL

Biodistribution and kinetic studies of technetium-99m labeled Naja naja karachiensis venom via gamma scintigraphic and SPECT images

Naja naja karachiensis have been responsible for plentiful deaths in Pakistan. To investigate bio distribution and blood kinetics, venom was labeled with the radiotracer [technetium-99m] by following the method of direct labeling technique. Its maximum labeling percentage was 97.7% [pH 6, 100microg stannous chloride clihydrate] which was higher than some other reported venom. Radio labeled venom was stable for more than 4 hours both in vivo [96%] and in vitro [serum 94.1%, saline 94.3%] experimentations. Intravenous doses of venom [250microg, 0.5mCi] were found to be evenly distributed [having R/L ratio=1.0] in all parts of sacrificed rabbits. Kidneys [53.75% activity/g] and urinary bladder [23.70% activity/g] were found with the copious quantity of injected dose of venom. Rest of all other organs was found with subsequent remaining dose of venom. Among them, lungs [14.2% activity/g], liver [4.32% activity/g], bones [1.38% activity/g], heart [0.8% activity/g], blood]0.56% activity/g], skin[0.45% activity/g] intestines [0.35% activity/g], skeleton muscles [0.3% activity/g], brain [0.14% activity/g] and stomach [0.05% activity/g] are included. After 24 hours of injection, poisoned blood of rabbits was almost cleared from venom. Gamma scintigraphic images [up to 2 hours] along with bio distribution suggest that kidneys are main organs of excretion in rabbits. Elimination started immediately after administration of venom however, possible sites for metabolism of venom are liver and lungs. More accumulation of venom in heart compared to brain suggests its higher affinity [thus possible higher toxicity] to cardiac muscles as compared to brain tissues

Hypertensive patients' readiness to use of mobile phones and other information technological modes for improvingtheir compliance to doctors' advice in Karachi

To determine the use of information technology [IT] and electronic media for improving compliance rate to doctors' advice in hypertensive patients in Karachi. Total 400 persons [200 males and 200 females] were randomly selected in six districts of Karachi. Data was collected through a pretested questionnaire. Following was sample criteria: age above 15 years, living in Karachi and ambulatory. Persons admitted in a hospital, individuals who were doing some physical activity during survey e.g. exercise, labor work etc., individual in stressed condition, non-cooperative individuals - not willing to get BP checked and fill questionnaire, and pregnant women were excluded. Those who did not sign the consent form were also excluded. SPSS was used for data analysis and descriptive statistics was employed for sensitivity analysis. For healthcare awareness, people look for health programs on radio and TV channels. Short Message Service [SMS] and phone are highly appreciated by patients for reminders. To increase compliance to doctors' advice, less educated people prefer phone calls over SMS whereas educated individuals favor SMS. Although price of medicine has not emerged as a major contributing factor for non-compliance, discount on medicinal products is highly appreciated by the patients. The study concludes that there is a widespread awareness of high blood pressure in the sample population of Karachi e.g. 72.5%. People consider reminder message system i.e. Calls and Short Messaging Service [SMS] would help them in improving compliance to doctors' advice

Comparative evaluation of various solubility enhancement strategies for furosemide

Drugs with good solubility exhibit good oral absorption, and subsequently good bioavailability. Thus, most exigent phase of drug development practice particularly for oral dosage forms is the enhancement of drug solubility. This review describes various traditional and novel methodologies proposed for the solubility enhancement of furosemide. For furosemide, solubility and permeability are crucial rate limiting factors to achieve its desired level in systemic circulation for pharmacological response. Thus, problematic solubility of furosemide is one of the main challenges for dosage form developing researchers. Various procedures, illustrated in this review, have been successfully employed to improve the furosemide solubility; however successful improvement essentially depends on the assortment of technique. It is concluded from the results that dissolution rate of drug increases by increasing the quantity of solubility enhancer. Dissolution rate also depends upon the type of enhancer and dissolution medium. In order to achieve relatively enhanced percentage drug release after 30 min [DP[30]], complexation by solvent evaporation using beta-cyclodextrin is the best method. Solid dispersion is found the best if polyethylene glycol is used as enhancer along with microcrystalline cellulose as hydrophilic adsorbent. All the approaches narrated in this article possess good perceptions for additional research i.e. in-vivo studies should be carried out focusing on delivery system development

Characterization and biological studies of bis- and tera-acetyl derivatives of hydrocarbon-bridged Diamines-I

A systematic study of the pharmaceutically important, double ended, chelating agents of the types CH[3]CONH [CH[2]] nNHCOCH[3] and [CH[3]CO] [2] N [CH[2]] n N[COCH[3]] [2], where n= 2, 3, 4, 5 and 6, prepared by the bis- and tetra-acetylation of the corresponding diamino-polymethylenes, have been carried out. Bis- and tertra-acetyl derivatives have been characterized by their elemental analysis and the FTIR spectra, Mass spectra and H-NMR spectra of these compounds have been reported to establish their structures. In the present work, FTIR spectra have been found an excellent means for distinguishing the bis-acetyl derivatives from their tetra-acetyl counterparts. The structures of these bis- and tetra-acetyl compounds have further been established by their H-NMR and Mass Spectra. The selective pharmacological screening of the derivatives was carried out according to the standard procedures. The compounds were screened for their antibacterial and antifungal activities and it was found that majority of these compounds did not possess any remarkable activity. Only the compound BA1, 2-DAE, showed significant antifungal activity against Microsporum canis [80%]

Synthesis, conjugation and evaluation of some novel polymers and their micro particles for sustained release drug formulations

To prepare and evaluate three novels functionalized polymers [PGA, PGA-co-caprolactone and PGA-copentadecalactone] for the development of nanoparticles which were further used in the development of a novel polymeric prodrug using Ibuprofen as a model drug. The Ibuprofen-polymer prodrug was developed by coupling the drug to one of the three prepared polyester polymers via ester linkage. A hydrolytic enzyme was used to prepare two polymer monomers, glycerol and polyvinyl adipate, which are non toxic, ester linked biological monomers. The polymers and their prodrug were characterized using NMR, GPC, UV-spectrophotometer and DSC. In vitro drug release study of Ibuprofen-polymer conjugate was performed in phosphate buffer PH 7.4 using a roller [Stuart STR 1] placed in an incubator [Stuart SI 60] and the temperature was kept constant at 37 +/- 1°C. Among the three polymers, glycerol-adipateco-pentadecalactone was observed to give a burst release following slow release in the medium. These characteristics suggest that these polymers can be successfully used in sustained release drug formulations

Formulation development and investigation of ibuprofen controlled release tablets with hydrophilic polymers and the effect of co-excipients on drug release patterns

The aim and objective of the present study was to formulate and evaluate controlled release polymeric tablets of Ibuprofen with determinations of formulation factors using various grades and types of polymer Ethocel i.e. Ethocel Standard 10P; 10FP, 100P and 100FP for their release rates and release patterns in suitable media and also the mechanism involved in the release of drug from the matrices. The effect of several co-excipients was also studied on the drug release rates and patterns of Ibuprofen from the polymeric matrices. Ibuprofen-Ethocel CR tablets were prepared at three different D:P ratios i.e. 10:1, 10:2 and 10:3. The effects of co-excipients were studied only in formulations having D:P ratio of 10:3. In vitro drug release studies of Ibuprofen-Ethocel controlled release matrix tablets were carried out in phosphate buffer pH 6.8 using Pharma Test Dissolution Apparatus adopting Rotating Basket Method according to USP. Different kinetic models were applied to the release data of test formulations in order to investigate the release mechanism of drug from the controlled release matrix tablets. The release patterns of Ibuprofen-Ethocel CR matrices were compared with reference conventional Ibuprofen tablets and Ibuprofen SR tablets. F[2] similarity factor was applied to the test formulations and reference standard to compare their similarities. The drug formulations studied exhibited satisfactory release results