ABSTRACT
Amorphous solid dispersions (ASDs) consisting of acetaminophen (APAP) and copovidone were systematically studied to identify effects of drug loading and moisture content on mechanical properties, thermal properties, and tableting behavior. ASDs containing APAP at different levels were prepared by film casting and characterized by differential scanning calorimetry and nanoindentation. The glass transition temperature (Tg) continuously decreased with increasing amount of APAP, but the hardness of ASDs was increased at a low APAP content and reduced at high APAP content. This in turn significantly influenced tablet quality. Water reduced both the hardness and Tg of ASDs, and the APAP loading level corresponding to the transition to the softening mechanism was lower at a higher relative humidity. Overall, the mechanical properties, rather than the thermal properties, better represent the plasticization/antiplasticization effect of small molecule to ASDs.
Subject(s)
Acetaminophen/administration & dosage , Analgesics, Non-Narcotic/administration & dosage , Pyrrolidines/chemistry , Vinyl Compounds/chemistry , Acetaminophen/chemistry , Analgesics, Non-Narcotic/chemistry , Crystallization , Drug Compounding , Hardness , Humidity , Phase Transition , Solubility , Tablets , Transition Temperature , Water/chemistryABSTRACT
In this study, we first developed a modernized indentation technique for measuring tablet hardness. This technique is featured by rapid digital image capture, using a calibrated light microscope, and precise area-determination. We then systematically studied effects of key experimental parameters, including indentation force, speed, and holding time, on measured hardness of a very soft material, hydroxypropyl cellulose, and a very hard material, dibasic calcium phosphate, to cover a wide range of material properties. Based on the results, a holding period of 3min at the peak indentation load is recommended to minimize the effect of testing speed on H. Using this method, we show that an exponential decay function well describes the relationship between tablet hardness and porosity for seven commonly used pharmaceutical powders investigated in this work. We propose that H and H at zero porosity may be used to quantify the tablet deformability and powder plasticity, respectively.