Dissolution

Rabeprazole sodium is a proton pump inhibitor used to treat peptic ulcer, duodenal ulcer, gastro oesophageal reflux disease by inhibiting the enzyme H+ /K+ATPase, the acidic pump. It is also used to treat Zollinger-Ellison syndrome, erosive esophagitis. This study is aimed to develop pharmaceutically equivalent and stable enteric-coated tablets of Rabeprazole sodium comparable to innovator product. The present work aims to avoid degradation of drug in acidic environment of stomach. Ten Formulations of Rabeprazole core tablets were developed using mannitol as diluents, magnesium stearate and talc as lubricant and glidant, Ethyl cellulose as seal coating, Eudragit L-30, Plasacrylic HTP, Instacoat EN HPMC Pthalate as enteric coated. Among the ten uncoated tablet batches F9 obtained good drug release profile compared to innovator. So a batch F9 was selected for further steps of formulation i.e., sub coating and enteric coating. After enteric coated batches F9 was evaluated for acid resistance test and in-vitro dissolution test compared with innovator found to be suitable for Rabeprazole sodium delayed release tablet. The stability studies were conducted at 40oC/75% RH for 3 months.

The article aims at developing simple, fast and effective dissolution method for Dabigatran etexilate mesylate capsules by RP-HPLC and validate as per ICH guidelines. The optimized RP-HPLC method for dissolution studies uses a reverse phase column, Phenomenex Luna C18 (250 X 4.6 mm;5μ), a mobile phase of triethylammonium phosphate buffer (pH 3.0):acetonitrile in the proportion of 40:60 v/v, diluent as 0.01N HCl, flow rate of 1.0ml/min, injection volume as 20µl. and a detection wavelength of 341nm using a UV detector. The optimized dissolution conditions include, 0.01N HCl as dissolution media, apparatus as USP Type 1 Basket, rpm as 100, dissolution media temperature as 37±0.5ºC, dissolution volume as 500ml, dissolution time point as 30mts, working concentration of standard and sample as 5µg/ml and a detection wavelength of 341 nm. The developed method resulted in Dabigatran etexilate exhibiting linearity in the range 1.25-10μg/ml. System precision and intra-day precision is exemplified by relative standard deviation of 1.59% and 2.21% respectively. Method was found to be rugged/inter day precise as %RSD was found to be 3.25. Percentage Mean recovery was found to be greater than 80% at all the three levels by absolute method during accuracy studies. LOD and LOQ for Dabigatran etexilate were found to be 0.05ng/ml and 5ng/ml respectively. Hence it can be concluded that effective dissolution method by RP-HPLC is developed and validated as per ICH guidelines which can be applicable in various pharmaceutical industries.

The objective of the present study was to enhance the dissolution profile, absorption efficiency of water insoluble drugs like Telmisartan. A novel “Powder Solution Technology” involves absorption and adsorption efficiency, which makes use of liquid medications admixed with suitable carriers and coating materials and formulated into a free flowing, dry looking, non adherent and compressible powder forms. Based upon a new mathematical model expression improved flow characteristics and hardness of the formulation has been achieved by changing the proportion of carrier and coating material ratio from 15:1 to 5:1. Avicel ® PH 102 was showing acceptable flow properties compared with Avicel ®PH 200. Higher dissolution rates were observed in optimized liquisolid formulation containing Poly ethylene glycol 400 and Avicel ®PH 102 compared with marketed product (SARTAN® 20mg tablets). Poly ethylene glycol 400 was showing highest solubility compared with poly ethylene glycol 200, propylene glycol and glycerin.The crystalline state of telmisartan drug state was changed to amorphous state due to liquisolid formation and was confirmed by both X-ray diffraction and Fourier transform infrared spectroscopy results, this transition occur as the drug is in solution form. Additionally, increasing the wetting properties and subsequent surface area of the drug available for dissolution.

Poor aqueous solubility of drugs is a major limiting factor with many new drugs in their successful launch in market in spite of their potential pharmacokinetic activity. Poorly water soluble drugs are becoming a problem in terms of obtaining satisfactory dissolution within the gastro intestinal tract, which is necessary for good bioavailability. Poorly water-soluble drugs are associated with slow drug dissolution followed by slow absorption leading eventually to inadequate and variable bioavailability. Various approaches to overcome the poor aqueous solubility of drugs have been investigated like solid dispersion, spherical agglomeration, nanoparticles, nanosuspensions, nanomorphs, nanocrystals, micronization, polymorphism, co-solvency, pH adjustment, use of surfactants, microemulsion, complexation. In this article, the basic approaches for enhancement of solubility and dissolution of poorly water-soluble drugs have been reviewed with literature-based examples of the formulation options for poorly water-soluble compounds and their practical applications to the industrial practices.

The present research work was aimed to enhance the solubility and dissolution rate of Olanzapine using Poloxamer as carrier by preparing solid dispersion. The solid dispersions and physical mixtures prepared was also evaluated  for the drug content and percentage drug yield and characterization of prepared systems is done with the help of in-vitro drug release, FTIR, XRD and DSC analysis. The results obtained showed that the percentage yield and percentage drug content was 98.32% and 99% respectively. It was clear that there was no loss of drug and polymer. The rate of dissolution of the drug in the case of solid dispersions was much enhanced as compared to the pure drug and their physical mixtures. FTIR spectra showed that there was not any interaction or hydrogen bonding between the drug and polymers in solid dispersions as well as physical mixtures. The polymorphic changes were studied with the XRD gave the idea that the solid dispersions were quite amorphous in nature as compared to the pure drug. In the diffraction pattern for solid dispersions, the number of crystalline peaks due to drug had disappeared. DSC showed that there was shifting in melting endotherm of drug in case of solid dispersion. From the XRD and DSC it was confirmed that the increase in the solubility and dissolution rate was due to polymorphic transition of drug from crystalline to amorphous form.

This study investigated the spherical agglomeration of itraconazole for enhanced drug dissolution rate and bioavailability at various polymers percentage like 0.2%, 0.4%and 0.6% with Soluplus®, HPMC and PEG-4000 by simple stirring at 900 r.p.m. (The spherical agglomerates(SA) were dried powdered and with method followed by characterized by differential scanning calorimetry and X-ray powder diffraction. The SAs of itraconazole were also evaluated by drug content study, solubility study and in-vitro dissolution study. The pharmacokinetic studies of the formulations and pure itraconazole were evaluated i.e. Cmax, Tmax and AUC   in vivo study by pharmacokinetic model on wistar rats.

A simple, specific, accurate and precise reverse phase high performance liquid chromatographic method has been developed for determination (drug release) of Citicoline in controlled release tablet dosage form by reverse phase separation was carried out on a columns containing different stationary phases, the final choice giving satisfactory theoretical plates and tailing with good reproducibility and run time, with dimension 250 mm × 4.6 mm internal diameter, 5-μm particle; Zorbax C18 reversed-phase column. The mobile phase consisting of buffer: methanol (95:5, pH 6.0) at a flow rate of 0.8mL/min. The UV detection wavelength was set at 270nm. The retention time for Citicoline was found to be 6.4 min. and recoveries from controlled release tablet dosage form were between 99.7% and 104.4%. The method was validated for specificity, linearity, accuracy, precision and robustness. The proposed method was optimized and validated as per the ICH guidelines. Key words: Citicoline monosodium, Reverse Phase -High performance liquid chromatography, Dissolution, Validation.

The aim of this study is to enhance the solubility of poorly water soluble drugs via the mixed hydrotrophic solid dispersion strategy using ibuprofen as a model drug because Ibuprofen is absorbed after oral administration, it is critical to improve the dissolution rate to enhance the bioavailability, due to its low water solubility. Solid dispersions were prepared by mixed hydrotrphic method. In vitro dissolution studies showed remarkable improvement in solubility and drug dissolution profile of these new ibupro­fen solid dispersions over pure ibuprofen. It was observed that dissolution rate of ibuprofen enhanced to a great extent by solid dispersion technique using citric acid and urea as a hydrotrophic agents.The results indicates that mixed hydrotrophic solid dispersion may serve as a successful strategy for enhancing solubility of poorly water soluble drugs.

The objective of the present study was to formulate a solid self micro emulsifying of drug delivery system (SMEDDS) for oral administration to improve the solubility and bioavailability of Lamotrigine. Solubility was determined in various oils, surfactants and cosurfactants. Ternary phase diagrams were constructed to evaluate the micro emulsification existence area. The optimized formula is obtained by factorial design employed as statistical tool.  The optimal formulation consists of 20% Capmul MCM C8, 55% Labrasol , 25% Tween 80 was adsorbed on carriers Aerosil200, Microcrystalline cellulose (MCC) .The solid SMEDDS are characterized by globule size analysis, and drug release studies of formulations are compared with plain drug. The pharmacokinetic study in rats for the optimized formulation was performed and compared to plain drug powder. SMEDDS have significantly increased the Cmax and area under the curve (AUC) of Lamotrigine compared to powder (P < 0.001). Thus, this self-micro emulsifying drug delivery system should been effective oral dosage form for improving oral bioavailability of Lamotrigine. Key Words: Solid self-microemulsifying drug delivery system, Globule size, Dissolution, Oral bioavailability  

  Stress is a biological response to aversive conditions that tend to threaten or perturb the homeostasis of the organisms. Stress is one of the basic factors in the etiology of number of diseases and stress has been postulated to be involved in pathogenesis of various diseases, such as psychiatric disorders like depression and anxiety, immune suppression, endocrine disorder like diabetes mellitus, impotency, cognitive dysfunction, peptic ulcer, ulcerative colitis and cardiovascular disorder like atherosclerosis and hypertension. So a mixture of herbal extracts like Arjuna, Ashwagandha, Brahmi and Shankhapushpi in equal ratios was microencapsulated using different types of wall polymers by non solvent addition method. Microcapsules were evaluated for their percentage yield, percentage actual drug content, percentage extract entrapment efficiency, flowability and drug release kinetics. Kollicoat SR 30 D and aluminium stearate were observed as effective in prevention of particle aggregation during phase separation.  Microcapsules were shown controlled drug release pattern for 12 hours due to the presence of Eudragit RS 100 and Eudragit RL 100. Both these wall polymers are responsible for controlling the drug release from microcapsules through diffusion in phosphate buffer medium having pH 7.4.