Improvement in the dissolution profile of diacerein using a surfactant-based solid dispersion technique.

In an attempt to improve the dissolution rate of poorly aqueous soluble diacerein (DCN), solid dispersions (SDs) were prepared with a surfactant Pluronic® F 127 (PXMR) at drug to polymer ratios of 1:0.5, 1:1.5, and 1:2.5 (w/w) by an ordinary melting technique. The interaction of DCN with PXMR in all solid binary systems was evaluated by thin layer chromatography (TLC), Fourier transform infrared spectrometry (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) studies. TLC indicated an absence of chemical interaction of DCN with PXMR whereas FTIR studies demonstrated an existence of strong hydrogen bonding between them. A uniform molecular dispersion of DCN was observed in DSC thermograms, and this finding was further supported by loss of the crystalline and irregular shape of DCN detected in SEM photomicrographs. Dissolution studies were promptly conducted to examine the release rate performance of DCN from all binary systems. The drug dissolution properties of binary systems improved significantly in comparison to crystalline DCN. The rate and extent of DCN release were observed to be strongly dependent on the proportion of PXMR present within the formulations.

Influence of Simulated Gastrointestinal Fluids on Polymorphic Behavior of Anhydrous Carbamazepine Form III and Biopharmaceutical Relevance.

The dissolution behavior and bioavailability of carbamazepine (CBZ) is rate-limited by formation of carbamazepine dihydrate (CBZ-D) in dissolution fluids. The present investigation involves formation and biopharmaceutical evaluation of CBZ-D obtained from simulated gastrointestinal fluids. The results obtained from solubility studies revealed that formation of CBZ-D was pH-dependent. The minimum solubility of 115 ± 1.7 mg/L obtained with simulated gastric fluid without pepsin indicates that the strongly acidic pH favors formation of CBZ-D and it was confirmed by the powder X-ray diffractography. Differential scanning calorimetry thermograms of samples revealed formation of CBZ-D and subsequent transition of CBZ form I. The percentage relative crystallinty for dihydrate was found to be 77.51%. Triton X present in fasted-state simulated gastric fluid (FaSSGF) increased the extent of crystallinty in dissolution media upto 86.50%. However, CBZ-D obtained from FaSSGF showed highest solubility of 335.36 ± 4.813 mg/L and dissolution of 36.74% in 60 min. This may be due to presence of surfactant on the surface of CBZ-D. The linear correlation was established between pH of simulated gastrointestinal fluids and percentage relative crystallinty with a correlation coefficient of 0.9904. CBZ form I had a better dissolution profile than any of the other polymorphs. Stabilization of CBZ form I in in vitro and in vivo conditions using pharmaceutical polymers in dosage form may bring better clinical outcomes than present-day therapies.

Formulation development and in vitro antioxidant studies of Churnas containing natural sweetener and nutraceutical.

Gymnema sylvestre, Curcuma longa, Azadiracta indica, Aegle marmelos, Salacia chinensis, Emblica officinalis were used as active components and Stevia rebaudiana as natural sweetener with nutraceuticalfor development of Churnas. The free radical scavengingpotential of Churnas was studied by using different antioxidant models of screening. The hydroalcoholic extract of sweet and bitter Churnas at 500µg/ ml showed maximum scavenging of the riboflavin NET system, DPPH and total antioxidant capacity. However, the extract showed only moderate scavenging activity of nitric oxide radicals and iron chelation. This could be due to higher phenolic content in the extract. Sweetness potency of Churna was found to be appropriate sweet, acceptable and palatable. These observations can be useful for the justifications of various ingredients and therapeutic applications of the Churnas.

Formulation and in vitro Evaluation of Floating Capsules of Theophylline.

Sustained release floating capsules for theophylline were fabricated using drug:polymer ratio of 30:70. The hydrocolloids were used in different proportions and four formulations were prepared. These formulations were optimized on the basis of buoyancy, matrix integrity, duration of floating and in vitro drug release. All the four formulations showed good buoyancy and matrix integrity. The duration of floating was more than 12 h for all formulations. In vitro drug release study of these formulations indicated controlled release of theophylline and about 76 percent drug was released at the end of 12 h.

Cardiotonic activity of aqueous extract of heartwood of Pterocarpus marsupium.

The present study was undertaken to evaluate cardiotonic activity of aqueous extract of heartwood of P. marsupium. This plant species contains 5,7,2-4 tetrahydroxy isoflavone 6-6 glucoside which are potent antioxidant and are believed to prevent cardiovascular diseases. Cardiotonic effect of aqueous extract of heartwood of P. marsupium was studied by using isolated frog heart perfusion technique (IFHP). Calcium free Ringer solution was used as vehicle for administration of aqueous extract of P. marsupium as a test extract and digoxin as a standard. A significant increase in height of force of contraction (positive inotropic effect) and decrease in heart rate (negative chronotropic effect) at a very low concentration (0.25 mg/ml) was observed with test extract as compared to the same dose of a standard digoxin. The present results indicated that a significant increase in height of force of contraction with decrease in heart rate was observed as the dose of test extract increased. The test extract produced cardiac arrest at 4 mg/ml, a higher concentration, as compared to standard, digoxin (0.5 mg/ml). Compared to digoxin, a drug with narrow therapeutic window, P. marsupium showed wide therapeutic window.

Non-enzymatic glycation of proteins: a cause for complications in diabetes.

Diabetes mellitus is one of the most common non-communicable diseases, and is the fifth leading cause of death in most of the developed countries. It can affect nearly every organ and system in the body and may result in blindness, end stage renal disease, lower extremity amputation and increase risk of stroke, ischaemic heart diseases and peripheral vascular disease. Hyperglycemia in diabetes causes non-enzymatic glycation of free amino groups of proteins (of lysine residues) and leads to their structural and functional changes, resulting in complications of the diabetes. Glycation of proteins starts with formation of Shiff's base, followed by intermolecular rearrangement and conversion into Amadori products. When large amounts of Amadori products are formed, they undergo cross linkage to form a heterogeneous group of protein-bound moieties, termed as advanced glycated end products (AGEs). Rate of these reactions are quite slow and only proteins with large amounts of lysine residues undergo glycation with significant amounts of AGEs. The formation of AGEs is a irreversible process, causing structural and functional changes in protein leading to various complications in diabetes like nephropathy, retinopathy, neuropathy and angiopathy. The present review discusses about role of glycation in various complications of diabetes.

Role of protein tyrosine kinase inhibitors in cancer therapeutics.

Protein tyrosine kinases (PTKs) are critical in regulating cell growth and differentiation and are deeply involved in several cancers. PTK-inhibitors are mainly ATP-site directed and are finding use in the treatment of several cancers, and more than 30 such agents are now in phase I-III clinical trials. The present review focuses mainly on the development of PTK inhibitors in clinical trials, with special emphasis on imatinib mesylate, a rationally designed, potent oral anticancer agent and selective inhibitor for Abl tyrosine kinase, including Bcr-Abl, C-kit and platelet-derived growth factor-receptor tyrosine kinases, which has been implicated in several malignancies, including chronic myeloid leukemia and gastrointestinal stromal tumour.

Liquid membrane phenomenon in diuretics.

Surface activity and critical micelle concentrations are reported for two diuretic drugs, furosemide and triamterene. The drugs generate a liquid membrane on a supporting membrane. Transport of chloride, sodium, and potassium ions through the liquid membranes generated by the drugs was studied. The data suggest that the phenomenon of liquid membrane formation may contribute to the diuretic action.

Liquid membrane phenomenon in reserpine action.

Reserpine was shown to generate a liquid membrane. Transport of adrenaline, noradrenaline, dopamine, 5-hydroxytryptamine, glutamic acid, and gamma-aminobutyric acid in the presence of the reserpine liquid membrane was studied. The data indicate that the phenomenon of liquid membrane formation is likely to play a role in the mechanism of reserpine action.

Liquid membrane phenomena in chlorpromazine action.

Chlorpromazine has been shown, in the present study, to generate a liquid membrane at an interface in accordance with Kesting's hypothesis [5]. The specific orientation of chlorpromazine molecules in a liquid membrane with hydrophobic ends facing the permeable substances has been found to reduce the permeability of catecholamines and neurotransmitter amino acids. This observation is discussed in the light of the orientation of receptor proteins in general. The data on transport of catecholamines and neurotransmitter amino acids are discussed in the context of the mechanism of action of chlorpromazine.

Liquid membrane phenomena in haloperidol action.

Haloperidol, a surface-active neuroleptic drug, was shown to generate a liquid membrane on a supporting membrane. Transport of adrenalin, noradrenalin, dopamine, serotonin, histamine, glutamic acid, gamma-aminobutyric acid, and sodium, potassium, and calcium ions through the haloperidol liquid membrane was studied. The data indicate that the phenomenon of a liquid membrane plays a significant role in the mechanism of action of haloperidol.