Spherical crystallization: A technique use to reform solubility and flow property of active pharmaceutical ingredients.

Tablets have been choice of manufacturers over the years due to their comparatively low cost of manufacturing, packaging, shipping, and ease of administration; also have better stability and can be considered virtually tamper proof. A major challenge in formulation development of the tablets extends from lower solubility of the active agent to the elaborated manufacturing procedures for obtaining a compressible granular material. Moreover, the validation and documentation increases, as the numbers of steps increases for an industrially acceptable granulation process. Spherical crystallization (SC) is a promising technique, which encompass the crystallization, agglomeration, and spheronization phenomenon in a single step. Initially, two methods, spherical agglomeration, and emulsion solvent diffusion, were suggested to get a desired result. Later on, the introduction of modified methods such as crystallo-co-agglomeration, ammonia diffusion system, and neutralization techniques overcame the limitations of the older techniques. Under controlled conditions such as solvent composition, mixing rate and temperature, spherical dense agglomerates cluster from particles. Application of the SC technique includes production of compacted spherical particles of drug having improved uniformity in shape and size of particles, good bulk density, better flow properties as well as better solubility so SC when used on commercial scale will bring down the production costs of pharmaceutical tablet and will increase revenue for the pharmaceutical industries in the competitive market. This review summarizes the technologies available for SC and also suggests the parameters for evaluation of a viable product.

In vitro and in vivo evaluations of ketoprofen extended release pellets prepared using powder layering technique in a rotary centrifugal granulator.

In the present study, an extended release pellet dosage form of ketoprofen was prepared using powder layering technique. A combination of ethyl cellulose (45 cps) and shellac polymers was used as a binder (12% w/w polymer) during drug layering and an extended release coating (1:3 ratio at 2%, 4% and 7% w/w polymer) within the same apparatus. The coated pellets were characterized for sphericity, Hardness-Friability Index, and drug content, and also underwent scanning electron microscopy. In vitro dissolution was performed in 900 mL of phosphate buffer (pH 6.8) using paddle apparatus at 100 rpm. Ethyl cellulose and shellac when used as binders during drug loading did not extend ketoprofen release beyond 3 h. However, coating of the drug loaded pellets using ethyl cellulose and shellac resulted in an extended release profile of about 10 h. Using Higuchi's model and the Korsmeyer equation, the drug release mechanism from the pellets was found to be an anomalous type involving diffusion and erosion. Scanning electron microscopy was used to visualize the pellet morphology and drug release mechanism during dissolution testing. In vivo evaluations of the extended release pellets in rats indicated a significant increase in the time to reach maximum concentration (t(max)) and extent of absorption (AUC(0-∞)) compared to the ketoprofen immediate release tablet blend dispersed and dosed. In conclusion, extended release pellets of ketoprofen could perform therapeutically better than conventional dosage forms, leading to improved efficacy for a prolonged period.

Development and in vitro evaluation of ketoprofen extended release pellets using powder layering technique in a rotary centrifugal granulator.

Powder layering technique was evaluated using laboratory scale centrifugal granulator instrument to prepare extended release pellet dosage form of ketoprofen. Ethyl cellulose and shellac polymers were used for drug layering and extended release coating in the same apparatus. Inert sugar spheres were intermittently treated with drug powder and binding solution. Combination of ethyl cellulose (45cps) and shellac was evaluated as binders at different levels (1:3 ratio, at 6%, 12%, 16% and 21%w/w polymer) for drug loading and for extended release coating (1:3 ratio at 2%, 4% and 7% w/w polymer). Pellets were evaluated for drug release study using paddle apparatus in pH 6.8 Phosphate buffer, 900ml at 100 rpm. Ethyl cellulose and shellac when used as binder during drug layering did not extend the ketoprofen release beyond 4h. However, coating of drug loaded pellets using ethyl cellulose and shellac resulted in extended release profile of ketoprofen for about 10h. Ethyl cellulose coating alone at a level of 3% w/w resulted in extended release profile. Coated pellets were evaluated for sphericity, Hardness-Friability Index and scanning electron microscopy. Scanning electron micrographs of the pellets showed a uniform coating of polymer on the core pellets substantiating the use of centrifugal granulator for extended release coating. Release pattern from the optimized batch was best explained by Higuchi's model. The drug release pattern from the pellets was found to be Non-Fickian anomalous type, involving both diffusion and erosion mechanism. Accelerated stability study of the coated pellets filled in hard gelatin capsule was conducted for 3-month period and observed for the effect on drug release profile.

Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations / Liberação prolongada prometazina HCl utilizando polímeros acrílicos por liofilização e técnicas de secagem por aspersão: consideração de formulação

The present study investigated a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RL100 and Eudragit S100 in different weight ratios (1:1 and 1: 5), and in combination (0.5+1.5), using freeze-drying and spray-drying techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM), as well as solubility and in vitro dissolution studies in 0.1 N HCl (pH 1.2), double-distilled water and phosphate buffer (pH 7.4). Adsorption tests from drug solution to solid polymers were also performed. A selected solid dispersion system was developed into capsule dosage form and evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of spray-dried dispersions were related to increasing amount of polymers, while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RL100 had a greater adsorptive capacity than Eudragit S100, and thus its combination in (0.5+1.5) for S100 and RL 100 exhibited a higher dissolution rate with 97.14 percent drug release for twelve hours. Among different formulations, capsules prepared by combination of acrylic polymers using spray-drying (1:0.5 + 1.5) displayed extended release of drug for twelve hours with 96.87 percent release followed by zero order kinetics (r²= 0.9986).

O presente trabalho compreendeu estudo de um novo sistema de liberação prolongada de cloridrato de prometazina (PHC) com polímeros acrílicos Eudragit RL100 e Eudragit S100 em diferentes proporções em massa (1:1 e 1:5) e em combinação (0,5+1,5), utilizando técnicas de liofilização e de secagem por aspersão As dispersões sólidas foram caracterizadas por espectrofotometria no infravermelho por transformada de Fourier (FT-IR), calorimetria diferencial de varredura (DSC), difratometria de raios X (PXRD), Ressonância Magnética Nuclear (RMN), microscopia eletrônica de varredura (SEM) e, também, por estudos de solubilidade e de dissolução in vitro em HCl 0,1 N (pH 1,2), água bidestilada e tampão fosfato (pH 7,4). Realizaram-se, também, testes de adsorção da solução do fármaco nos polímeros sólidos. Desenvolveu-se sistema de dispersão sólida exclusiva dentro das cápsulas, que foi avaliado por meio de estudos de dissolução in vitro. Relacionou-se o desaparecimento progressivo de picos do fármaco em perfis termotrópicos de dispersões secas por spray à quantidade aumentada de polímero, enquanto os estudos de SEM sugeriram dispersão homogênea do fármaco no polímero. O Eudragit RL100 apresentou maior capacidade de adsorção do que o Eudragit S100 e, dessa forma, a combinação de (0,5+1,5) para S100 e para RL100 mostrou taxa de dissolução maior, com liberação de 94,17 por cento de fármaco em 12 horas. Entre as várias formulações, as cápsulas preparadas pela combinação de polímeros acrílicos utilizando secagem por aspersão (0,5+1,5) apresentou liberação prolongada do fármaco em 12 horas, com 96,78 por cento de liberação, seguindo cinética de ordem zero (r² = 0,9986).