PREPARATION AND EVALUATION OF PULSATILE DRUG DELIVERY OF FLUVASTATIN SODIUM

ABSTRACTIn the present study, an attempt was made to develop the pulsatile drug delivery of fluvastatin sodium to the colon. Formaldehyde-treated capsulebodies were used for the preparation of pulsincaps. It was sealed with a unhardened cap of the capsule. The microspheres were prepared by emulsionsolvent evaporation technique. Optimized microsphere formulations were selected based on dissolution studies. Hydrogel plug (HP) (Karaya gum andlactose in 1:1 ratio) having 4.5 kg/cm hardness and 100 mg weight was placed in the capsule opening and found that it was satisfactory to retard thedrug release in small intestinal fluid and to eject out the plugin colonic fluid and releasing the microspheres into colonic fluid after a lag time criterionof 5 hrs. The sealed capsules were completely coated by dip coating method with 5% cellulose acetate phthalate to prevent variable gastric emptying.Dissolution studies of pulsatile capsule device in media with different pH (1.2, 7.4 and 6.8) showed that drug release in the colon could be modulatedby optimizing the concentration of polymers in the microspheres. Drug-polymer interaction studies indicated no interaction in between the drug andthe polymer. Among all the formulations, fluvastatin sodium microspheres prepared with Eudragit RS 100 in 1:3 ratio shown prolonged release for aperiod of 12 hrs. The obtained results showed the capability of the system in delaying drug release for a programmable period of time and to deliverthe drug in the early morning hours when cholesterol synthesis are more prevalent.2Keywords: Fluvastatin sodium, Pulsatile, Hydrogel plug

An advanced draft genome assembly of a desi type chickpea (Cicer arietinum L.)

Chickpea (Cicer arietinum L.) is an important pulse legume crop. We previously reported a draft genome assembly of the desi chickpea cultivar ICC 4958. Here we report an advanced version of the ICC 4958 genome assembly (version 2.0) generated using additional sequence data and an improved genetic map. This resulted in 2.7-fold increase in the length of the pseudomolecules and substantial reduction of sequence gaps. The genome assembly covered more than 94% of the estimated gene space and predicted the presence of 30,257 protein-coding genes including 2230 and 133 genes encoding potential transcription factors (TF) and resistance gene homologs, respectively. Gene expression analysis identified several TF and chickpea-specific genes with tissue-specific expression and displayed functional diversification of the paralogous genes. Pairwise comparison of pseudomolecules in the desi (ICC 4958) and the earlier reported kabuli (CDC Frontier) chickpea assemblies showed an extensive local collinearity with incongruity in the placement of large sequence blocks along the linkage groups, apparently due to use of different genetic maps. Single nucleotide polymorphism (SNP)-based mining of intra-specific polymorphism identified more than four thousand SNPs differentiating a desi group and a kabuli group of chickpea genotypes

A draft genome sequence of the pulse crop chickpea (Cicer arietinum L.)

Cicer arietinum L. (chickpea) is the third most important food legume crop. We have generated the draft sequence of a desi-type chickpea genome using next-generation sequencing platforms, bacterial artificial chromosome end sequences and a genetic map. The 520-Mb assembly covers 70% of the predicted 740-Mb genome length, and more than 80% of the gene space. Genome analysis predicts the presence of 27 571 genes and 210 Mb as repeat elements. The gene expression analysis performed using 274 million RNA-Seq reads identified several tissue-specific and stress-responsive genes. Although segmental duplicated blocks are observed, the chickpea genome does not exhibit any indication of recent whole-genome duplication. Nucleotide diversity analysis provides an assessment of a narrow genetic base within the chickpea cultivars. We have developed a resource for genetic markers by comparing the genome sequences of one wild and three cultivated chickpea genotypes. The draft genome sequence is expected to facilitate genetic enhancement and breeding to develop improved chickpea varieties

Intranasal Cabergoline: Pharmacokinetic and Pharmacodynamic Studies

Aims of this investigation were to prepare and characterize cabergoline intranasal microemulsion formulations, determine brain drug delivery through biodistribution using technetium-99m (99mTc) as a tracer, and assess its performance pharmacodynamically in weight control. Cabergoline microemulsions of different compositions were prepared by water titration method and characterized for globule size and zeta potential. Microemulsion with maximum drug solubilization and stability was considered optimal and taken for further studies with or without addition of mucoadhesive agent. Pharmacokinetics of optimized 99mTc-labeled cabergoline formulations and 99mTc-labeled drug solution were studied by estimating radioactivity in brain and blood of albino rats post intranasal, intravenous, and oral administrations. To confirm localization of drug in brain following intranasal, intravenous, and oral administrations, gamma scintigraphy imaging was also performed. To assess weight control performance of formulations, body weight, white adipose tissue mass, serum lipids, leptin, and prolactin were determined before and after 40 days of intranasal administrations of these formulations to Wistar rats. Microemulsions were found to be stable both physically and chemically when stored at various stress conditions. Brain/blood uptake ratios, drug targeting efficiency, and direct drug transport were found to be highest for drug mucoadhesive microemulsion followed by drug microemulsion and drug solution post-intranasal administration compared to intravenous drug microemulsion. Significant (p < 0.05) reduction in assessed pharmacodynamic parameters was observed after intranasal administration of mucoadhesive microemulsion against control group. The results of the studies conclusively demonstrate that intranasal microemulsion formulations developed in this investigation are stable and can deliver cabergoline selectively and in higher amounts to the brain compared to both drug administrations as a solution intranasally or microemulsion intravenously. The results also demonstrate reduction in weight, adipose tissue mass, serum lipids, and serum prolactin after intranasal administration of drug microemulsion. Hence, long-term studies in at least two more animal models followed by extensive clinical evaluation can safely result into a product for clinical use