Lars Stubberud

Water solid interactions II. Effect of moisture sorption and glass transition temperature on compactibility of microcrystalline cellulose alone or in binary mixtures with polyvinyl pyrrolidone

The relation between the moisture sorption and compaction properties of microcrystalline cellulose, MCC, and binary mixtures of MCC with polyvinyl pyrrolidone, PVP, has been examined. PVP is a completely amorphous polymer, whereas MCC contains various fractions of amorphous structure depending not only on the quality used but also on the pharmaceutical processing. The tensile strength of tablets of MCC is shown to depend upon the relative humidity, RH, prior to compaction. At an RH of about 70%, a decrease in strength is observed corresponding to the upward shift of the moisture sorption isotherm. For a dry blend of MCC and PVP as well as for a granulation, the tensile strength is determined by the properties of MCC at humidities below 70% RH. At humidities above 70%, a reduction of the glass transition temperature of PVP below the operating temperature (20°C) is the dominating factor, resulting in a decrease in tensile strength.

Water-Solid Interactions. III. Effect of Glass Transition Temperature, Tg, and Processing on Tensile Strength of Compacts of Lactose and Lactose/Polyvinyl Pyrrolidone

The effect of moisture sorption at different relative humidities on the tensile strength and the physical stability of compacts of crystalline and partly amorphous lactose, alone and in binary mixtures with PVP, has been studied. Furthermore, the role of moisture as a plasticizer and its effect on the glass transition temperature, Tg, are related to the compactibiltiy. Samples were conditioned for 2 hr using a climate test chamber at different relative humidities. Moisture sorption was determined, the radial crushing strength for compacts was measured immediately and after storage, and the tensile strength was calculated. The glass transition temperature, Tg, was determined using DSC. The tensile strength of the compacts was found to depend on both the conditioning humidity and the humidity during storage. An increase in humidity to a level at which the glass transition temperature, Tg, fell below the operating temperature, T, resulted in transition from a rigid glassy state to a mobile rubbery state. For compacts of partly amorphous lactose, an increase in the tensile strength was observed during storage of tablets, due to recrystallization of the amorphous regions above Tg. Tablets of mixtures of lactose and PVP exhibit a sharp decrease in tensile strength at humidities above 70% RH, due to the glass-to-rubber transition of PVP.

Water-solid interactions. I: A technique for studying moisture sorption/desorption

Abstract Moisture sorption and desorption have been characterized for active (naproxen and paracetamol) and inactive pharmaceutical solids by using a climatic test chamber. The relative humidity (RH) of the climatic test chamber was varied in the range from 15 to 90%. Equilibrium moisture content was achieved within a period of 2 h for slightly hygroscopic and moderately hygroscopic substances. For very hygroscopic substances equilibrium was reached within 2 h at low RH ( 60%). Moisture sorption isotherms were characterized by using the climatic test chamber and were found to be identical with moisture sorption isotherms characterized by desiccators.

Water-Solid Interactions. IV. Influence of Moisture Sorption on the Compaction of Film-Coated Particles

The effect of moisture sorption on the compaction properties of model modified-release (MR) pellets coated with ethyl cellulose/hydroxypropylcellulose film has been studied for the MR pellets alone and in binary mixtures with microcrystalline cellulose, lactose alpha-monohydrate, or lactose 9% amorphous. The in vitro dissolution rate prior to and after compaction was used as an indirect method of evaluating the effect of exposing the MR pellets to a compaction force. Moisture sorption as well as the glass transition temperature (Tg) using differential scanning calorimetry (DSC) were determined as a function of humidity for cast film conditioned at different humidities using a climate test chamber. The compaction properties of lactose and microcrystalline cellulose were altered by the addition of MR pellets, resulting in a robust tablet mass and a tensile strength of the tablet masses that was less sensitive to moisture. The amount of moisture sorbed was found to have little influence on the formation of cracks or on the rupturing of film-coated MR pellets during compaction. This was probably a result of both the small depression in the Tg for the film system at increasing RH and the robustness of the film chosen. The results also showed that the volume reduction properties of the tableting excipients were of importance for reducing damage to the film coating. Lactose had a higher protective effect on the film-coated MR pellets compared to microcrystalline cellulose.