Enhanced dissolution of megestrol acetate microcrystals prepared by antisolvent precipitation process using hydrophilic additives (original) (raw)
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Pharmaceuticals
In this study, the effect of Cremophor® RH 40 (CR 40) classic micelles and Soluplus® (SP) polymeric micelles were investigated on a novel granule-type drug-delivery system containing megestrolacetate (MGA). Using a risk assessment-based approach on the formulation via melt technology resulted in the formation of these granules, presented as the dosage, with proper particle size and flow characteristics. Due to the application of a eutectic carrier base composition, gentle process conditions were reached, retaining the crystalline structure of the carrier system and allowing for the proper distribution of MGA in the granules. The increased water solubility (0.111 mg/mL to 2.154 mg/mL), and the decreased nano particle size (102.27 nm) with uniform distribution (polydispersity index of 0.259) and colloid stability (zeta potential of −12.99 mV) resulted in SP polymeric micelles prevailing over CR 40 micelles in this gastric dissolution study, performed in biorelevant fasted and fed stat...
Redispersible fast dissolving nanocomposite microparticles of poorly water-soluble drugs
International Journal of Pharmaceutics, 2014
Enhanced recovery/dissolution of two wet media-milled, poorly water-soluble drugs, Griseofulvin (GF) and Azodicarbonamide (AZD), incorporated into nanocomposite microparticles (NCMPs) via fluidized bed drying (FBD) and spray-drying (SD) was investigated. The effects of drying method, drug loading, drug aqueous solubility/wettability as well as synergistic stabilization of the milled suspensions on nanoparticle recovery/dissolution were examined. Drug nanoparticle recovery from FBD and SD produced NCMPs having high drug loadings was evaluated upon gentle redispersion via optical microscopy and laser diffraction. During wet-milling, hydroxypropyl cellulose (HPC) alone stabilized more wettable drug (AZD) nanoparticles with slight aggregation, but could not prevent aggregation of the GF nanoparticles. In contrast, well-dispersed, stable nanosuspensions of both drugs were produced when sodium dodecyl sulfate (SDS) and HPC were combined. The FBD and SD NCMPs without SDS exhibited incomplete nanoparticle recovery, causing slower dissolution for GF, but not for AZD, likely due to higher aqueous solubility/wettability of AZD. For high active loaded NCMPs (FBD ∼50 wt%, SD ∼80 wt%) of either drug, HPC-SDS together owing to their synergistic stabilization led to fast redispersibility/dissolution, corroborated via optical microscopy and particle sizing. These positive attributes can help development of smaller, high drug-loaded dosage forms having enhanced bioavailability and better patient compliance.
Objective: Propranolol HCl loaded microparticles was prepared using non-aqueous emulsification solvent evaporation technique having higher Encapsulation efficiency and slower the drug release. Nondegradable based on ammonio methacrylate copolymers containing the hydrophilic drug Propranolol HCl were prepared with an oil-in-oil (O/O) solvent evaporation technique by using Eudragit RSPO or Eudragit RLPO individually or in a combination of both polymer. Our objective was to apply this technique in order to develop highly water soluble drugs loaded microparticles with both these copolymers. Method: In the present work we have selected antihypertensive drug Propranolol HCl due to its short half life and highly water solubility for the preparation of sustained release microparticles using modified O/O Emulsion Solvent Evaporation method. The sustained release
2011
To prepare and evaluate comparatively the dissolution behaviour of metoprolol tartrate loaded PLGA (50:50) and PLGA (75:25) microparticles. Metoprolol tartrate loaded PLGA microparticles were prepared using non-solvent addition phase separation technique with drug to polymer ratio 1:1, 1:2 and 1:3. Metoprolol tartrate contents were determined spectrophotometrically at 273 nm. Drugpolymer compatibility was determined by FTIR, XRD and thermal analysis. Microparticle morphology was characterized by SEM.
ChemInform, 2013
The solubility and dissolution properties of drugs play an important role in the process of formulation development. More than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically insoluble in water. For orally administered drugs solubility is one of the rate-limiting parameter to achieve their desired concentration in systemic circulation for pharmacological response. Problem of solubility is a major challenge for formulation scientist, which can be solved by different technological approaches during the pharmaceutical product development which include physical and chemical approaches such as micronization, pH adjustment, solid dispersion, complexation, co-solvent, salt formation, nanotechnology, use of surfactant, hydrotophy, polymorphs. Proper selection of solubility enhancement method is the key to ensure the goals of a good formulation like good oral bioavailability, reduce frequency of dosing and better patient compliance combined with a low cost of production. The present review article focuses on the recent techniques of solubilization for the attainment of effective absorption and improved bioavailability of poorly water soluble drugs.
Poorly Water Soluble Drugs: Change in Solubility for Improved Dissolution Characteristics a Review
The aim of this review is to study various parameters to improve the solubility and bioavilability of poorly water soluble drugs. The oral route of administration is the most preferred and widely acceptable route of delivery due to ease of ingestion for many drugs. Drugs with slow dissolution rate show the incomplete absorption leading to low bioavilability when orally administered. Various approaches such as micronization, solid dispersion, complexation, hydrotrophy, co-solvency, use of surfactant, sonocrystallization, particle size reduction, micro emulsion, nanosuspensions, cryogenic Techniques has been used to enhance the solubility of poorly water soluble drugs. In this review authors discussed about various Techniques used to enhance absorption and bio avilability of drugs and various patents available on solubility enhancement.
2010
Mefenamic acid and Astemizole are models of drugs with poor aqueous solubility. The dissolution rates of Mefenamic acid and Astemizole were enhanced by the precipitation of both drugs in the presence of aqueous surfactant (SAA) (Cremophor®) and polymer solution (PEG 20,000). The highest dissolution rate for both drugs was achieved by precipitation in the presence of (Cremophor®), followed by precipitation in the presence of (PEG 20,000). The precipitated crystals were characterized using IR, DSC, SEM and X-ray powder diffraction. Mefenamic acid precipitates were of smaller size with no habit change, while in the case of astemizole there was a decrease in the crystallinity compared with the original powder. No changes in the polymorphic forms for both drugs were noticed during precipitation process.
Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs
International Journal of Pharmaceutics, 2006
Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, the melt emulsification method traditionally used to prepare solid lipid nanoparticles was adapted to produce drug nanosuspensions. The method was evaluated in comparison with the well known solvent diffusion process for ibuprofen as a model drug. Control of the preparation variables (stabilizers, drug content, homogenization procedure and cooling conditions) allowed formation of nanosuspensions with diameters less than 100 nm. The major advantage of the melt emulsification method over the solvent diffusion method is the avoidance of organic solvents during production, although the mean particle size is slightly greater. The combination of Tween 80 and PVP K25 as stabilizers yields nanosuspensions with the smallest average particle size. The formulation of ibuprofen as a nanosuspension, either in the form of lyophilized powder or granules, was very successful in enhancing dissolution rate, more than 65% of the drug being dissolved in the first 10 min compared to less than 15% of the micronized drug. The increase in in vitro dissolution rate may favourably affect bioavailability and improve safety for the patient by decreasing gastric irritancy.
A Literature Review for Improving the Solubility of Poorly Water-Soluble Drug
Nanocrystal technology has showed significant potential for commercial applications and advancements as a novel pharmacological method to increasing the water solubility of certain poorly soluble medicines. Nanotechnology is the most effective method for solving the solubility issues with medications in BCS classes II and IV. This article is primarily concerned with the methods of preparing nanocrystals by means of Precipitation Lyophilization Homogenization (PLH) Technology. In particular, emphasised combinative technology could improve particle size reduction. Technology, equipment, and medication physicochemical qualities affect particle size reduction success. Precipitation, Lyophilization and homogenization have been used to develop and commercialize poorly soluble pharmaceuticals. Combination techniques, such as those discussed in this review article (Precipitating water-insoluble drug nanocrystals; Synthesis of Drug Nanoparticles Using Antisolvent Precipitation; Lyophilization Process; Nanoparticles Loaded with Proteins and Lyophilized); have led to significant advances in the field of drug delivery Microfluidizers, Piston Gap Homogenizer and Applications of PLH. Their potential therapeutic effectiveness in comparison to conventional medications could be potentially enhanced by future needs for PLH technology. Nanomedicine's long-term success will rely on pharmaceutically-informed, rationally designed PLH technology and tools.