Physical Stability Of Tablets Research Articles

Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant

Amorphous forms of poorly soluble drugs are more frequently being incorporated into solid dispersions for administration and extensive research has led to a reasonable understanding of how these dispersions, although still kinetically unstable, improve stability relative to the pure amorphous form. There remains however a paucity of literature describing the effects on such solid dispersions of subsequent processing into solid dosage forms such as tablets. This paper addresses this area by looking at the effects of the addition of common excipients and different manufacturing routes on the stability of a spray-dried dispersion (SDD) of the cannabinoid CB-1 antagonist, ibipinabant. A marked difference in physical stability of tablets was seen with the different fillers with microcrystalline cellulose (MCC) giving the best stability profile. It was found that minimising the number of compression steps led to improved formulation stability with a direct compression process giving the best results. Increased levels of crystallinity were seen in coated tablets most likely due to the exposure of the amorphous matrix to moisture and heat during the coating process. DSIMS analysis of the SDD particles indicated increased levels of polymer on the surface.

Development of effervescent tablets containing benznidazole complexed with cyclodextrin

Benznidazole (BNZ), the primary chemotherapy agent used to treat Chagas disease, has poor aqueous solubility, which results in low bioavailability. The purpose of this work was to develop stable effervescent tablets using an inclusion complex of BNZ with cyclodextrin (CD). In the first phase, different CDs were evaluated according to their ability to improve the aqueous solubility of BNZ. Then, inclusion complexes of BNZ in the solid state were produced by the kneading method and the complexes were evaluated using several physical-chemical assays. Finally, effervescent tablets were prepared according to a complete 3(2) factorial design. The effects of the concentration of CD and effervescent mixture on the dissolution rate and physical stability of tablets were evaluated. Hydroxypropyl-β-cyclodextrin produced the greatest improvement in the aqueous solubility of BNZ, almost 20-times greater than the water system. Solid systems produced with BNZ and CD showed physical-chemical interactions and increased the drug dissolution rate, suggesting the formation of a true solid inclusion complex. Moreover, the effervescent matrix of the tablets was effective in improving the dissolution behaviour of BNZ complexed with CD. Effervescent tablets produced using an inclusion complex of BNZ with CD suggest a possible improvement in the bioavailability of BNZ, and this could represent a relevant advance in Chagas therapy.

Application of on-line Raman spectroscopy for characterizing relationships between drug hydration state and tablet physical stability

Experiments were conducted to elucidate the relationship between risedronate sodium (RS) hydration state and the physical stability of tablets containing RS. The RS crystal lattice contains channels occupied by water, which is removed by drying processes at temperatures below the boiling point of water, causing a reversible contraction of the crystal lattice. In this study, risedronate sodium was wet granulated followed by fluid bed drying to final granulation moisture contents between 1 and 7%, and then compressed into tablets. During drying, the RS solid-state form was continuously monitored using on-line Raman spectroscopy. Raman spectra acquired in these experiments enabled direct monitoring of changes in the RS crystal lattice, due to dehydration, which provided key information relating RS solid-state form characteristics to final granulation moisture content. Final granulation moisture was found to have a significant effect on the change in RS hydration state measured by Raman spectroscopy. As the final granulation moisture decreased, the amount of RS dehydrated form increased. The largest Raman spectral changes were in the C H stretching region and the region including the 3-picoline ring and PO 2 − stretches. These changes are indicative of substantial changes in the RS solid-state structure. Final granulation moisture also had a significant effect on the change in tablet thickness over time. Lower final granulation moisture caused a greater increase in tablet thickness as the RS rehydrated. In addition, the change in RS hydration state during fluid bed drying, measured by on-line Raman, was correlated to the increase in tablet thickness and subsequent loss of tablet integrity. Raman spectroscopy allowed direct RS hydration state monitoring, rather than inference from a bulk moisture measurement. Development of a Process Analytical Technology (PAT), specifically Raman, to monitor RS solid-state during drying enabled establishment of relationships between fundamental hydration dynamics associated with RS and final product performance attributes.

Effect of Amount and Composition of Granulating Solution on Physical Characteristics of Tablets

AbstractThe effect of granulating solution on the physical characteristics and physical stability of tablets was studied based on the response surface methodology. The amount of granulating solution, X1 and its composition ratio, X2, were selected as independent variables. The tablets (100 mg) were manufactured by compressing the mixture of each granule with disintegrant (4 %) and lubricant (0.5 %). A rotary tabletting machine was used. Several characteristics of tablets were well expressed as a quadratic function of X1 and X2 in coded levels. A computer optimization method was applied to the data generated, and a good agreement was observed between the predicted and experimental results in the optimal formula.

Evaluation of a novel cellulose powder as a filler-binder for direct compression of tablets

A novel form of cellulose powder was evaluated as a filler-binder in tablets. The particle, powder, flow and binding properties of this experimental cellulose material were compared with those of two commercial microcrystalline celluloses, Avicel PH 101 and Emcocel. The effect of various storage conditions on the physical stability of tablets compressed from celluloses was also evaluated. The particle size and shape of experimental cellulose powder differed markedly from those of microcrystalline celluloses. Experimental cellulose contained mainly large and roughly spherical agglomerates of particles, among which were few smaller regularly shaped particles. Because of spherical particle shape, the experimental cellulose powder flowed better than microcrystalline celluloses, which consisted of much more irregularly shaped particles. Experimental cellulose formed stronger tablets than microcrystalline celluloses. It also acted more effectively than microcrystalline celluloses as a binding material in tablets containing poorly compressible ascorbic acid and acetaminophenone. This may be due to the extensive surface area of the particles of experimental cellulose powder. The specific surface area of this material was over 50 times as great as that of microcrystalline celluloses. This indicates an extremely porous structure of cellulose agglomerates. Tablets containing experimental cellulose powder were able to resist a permanent loss in tablet strength at different storage conditions better than tablets containing microcrystalline celluloses. According to the results of this study an experimental agglomerated form of cellulose powder is a very advantageous material as a filler-binder for direct compression of tablets.

The Effect of Moisture on Powder Flow and on Compaction and Physical Stability of Tablets

The Effect of Moisture on Powder Flow and on Compaction and Physical Stability of Tablets

New Approach to Aqueous Granulation of Highly Hydrosoluble Drugs

AbstractThe critical effect of binding solvents in aqueous wet granulation,on the physicalstability of tablets was investigated. The implications of the shelfcementation process in aqueous granulation of Piracetam are discussed.

The Physical Stability of Tablets Coated using an Aqueous Dispersion of Ethylcellulose

AbstractFilms formed from an aqueous dispersion of ethylcellulose mixed with hydroxypropylmethylcellulose were deposited onto sodium bicarbonate, microcrystalline cellulose, and acetylsalicylic acid (ASA) tablets. Upon storage at elevated temperatures and relative humidity, no changes in disintegration times were observed with the sodium bicarbonate tablets or with tablets containing microcrystalline cellulose. Marked increases were observed in disintegration times with the ASA tablets, these increases being dependent on both temperature and relative humidity. Examination of films by scanning electron microscopy indicated that coalescence of particles within the films had occurred in those samples where increases in disintegration times were observed.

Physical and Chemical Stability Testing of Tablet Dosage Forms

The influence of excipients and lubricants on the chemical and physical stability of tablets is demonstrated. Tablet color stability and its measurement is reviewed. The applicability of chemical kinetic principles and the Arrhenius relationship to stability data for tablet systems is illustrated. The importance of the package to product stability is shown. The utility of exaggerated temperature, light, and humidity conditions in the stability testing of tablet dosage forms is demonstrated. The importance and significance of a well-organized stability testing program for evaluating the physical and chemical stability of solid dosage forms are discussed.