Effect of characteristics of compounds on maintenance of an amorphous state in solid dispersion with crospovidone.

Solid dispersion (SD) of indomethacin with crospovidone (CrosPVP) shows useful characteristics for preparation of dosage forms. This study aimed to determine the types of drugs that could adopt a stable amorphous form in SD. Twenty compounds with various melting points (70-218 degrees C), molecular weights (135-504) and functional groups (amide, amino, carbonyl, hydroxyl, ketone etc.) were prepared in SD with CrosPVP. The CrosPVP SDs were prepared using a mechanical mixing and heating method. Melting point and molecular weight were found to have no influence on the ability of a compound to maintain an amorphous state in SD. All compounds containing hydrogen-bond-donor functional groups existed in an amorphous state in SD for at least 6 months. Infrared spectra suggested an interaction between the functional groups of these compounds and amide carbonyl group of CrosPVP. Compounds without hydrogen-bond-donor groups could not maintain an amorphous state and underwent recrystallization within 1 month. It was suggested that the presence of a hydrogen-bond-donor functional group in a compound is an important factor affecting the stable formation of SD with CrosPVP, which contains a hydrogen-bond acceptor.

Fluidity and tableting characteristics of a powder solid dispersion of the low melting drugs ketoprofen and ibuprofen with crospovidone.

A powder solid dispersion system (SD) of ketoprofen (KP) or ibuprofen (IP), which possess low melting points, plus crospovidone (CrosPVP), have good fluidity characteristics and can be used to formulate tablets. Tablets of KP or IP in the SD of adequate hardness within a narrow weight range can be prepared by direct compression. Addition of microcrystalline cellulose (MCC) resulted in greater hardness characteristics and less variation in tablet weight. Forces during the tableting process were measured with a tableting process analyzer (TabAll) equipped with a single-punch for determining capping and sticking properties during the tableting process. Pressure transmission ratio from the upper to the lower punch and die wall force were increased by adding 1% magnesium stearate (MS) to the SD. Ejection force decreased when MS was added to the SD. When tablets of the IP SD were prepared without excipient, scraper pressure (SP) was large, resulting in sticking. However, addition of 1% MS, lowered the SP value and eliminated sticking. Thus, an SD of compounds with a low melting point such as KP or IP is suitable for tablet manufacture by direct compression with the addition of 1% MS.

Evaluation of the compaction properties of a solid dispersion of indomethacin with crospovidone by tableting process analyzer.

A powder solid dispersion system (SD) of indomethacin (IM) with crospovidone (CrosPVP) possesses good fluidity and can be used for tablet formulation. Tablets of SD can be prepared by direct compression and have adequate hardness and a small variation in weight. Forces during the tableting process were measured with a tableting process analyzer (TabAll) equipped with a single-punch. The pressure transmission ratio (PTR) from the upper to the lower punch and the die wall force (DWF) were examined during the tableting process. Ejection force (EF) and scraper pressure (SP) were measured for determining the capping and sticking properties during the tableting process. Adding 1% magnesium stearate (MS) to the SD resulted in high PTR and DWF values and a low EF value. PTR and DWF values increased and EF value decreased when MS and microcrystalline cellulose (MCC) were added to the SD. A thousand tablets could be manufactured without problems such as sticking or capping when 1% MS and 50% MCC were added to the SD containing 25% IM.

Preparation, characterization, and tableting of a solid dispersion of indomethacin with crospovidone.

A significant problem with solid dispersion (SD) systems is the difficulty in preparing dosage forms. This difficulty can be overcome using crospovidone (CrosPVP) as a carrier. A powder SD of indomethacin (IM) with CrosPVP was prepared using mechanical mixing followed by heating to temperatures below the melting point. IM and CrosPVP interacted to produce IM in an amorphous state when its concentration was <40%. The solubility of IM was improved about fourfold compared to IM crystal. The SD had good fluidity, and tablets were prepared by direct compression. Tablets with small weight variation and acceptable hardness were obtained using only 1% of magnesium stearate as excipient. The dissolution of IM from tablets was similar to that of SD powder because CrosPVP, a disintegration agent, caused the tablets to break up rapidly.