ABSTRACT
OBJECTIVE: The objectives of the current study were to understand the dissolution behaviors of amorphous solid dispersions (ASD) using different screening methods and their correlation to the dissolution of formulated products. MATERIALS AND METHODS: A poorly soluble compound, compound E, was used as a model compound. ASDs were prepared with HPMC, Kollidon VA64 and Eudragit EPO using hot-melt extrusion. Different techniques including precipitation, powder, capsule and compact dissolution and the dissolution of formulated products were conducted in USP simulated gastric fluid using a USP II dissolution apparatus. RESULTS AND DISCUSSIONS: It was found that a precipitation study could generally predict powder, capsule and compact dissolution. Yet, it was recommended to run the dissolution at a higher paddle speed or for a longer duration to improve the predictability. It was also recommended to run powder, capsule and compact dissolution at both slow and high speeds to gain insights into wetting, dispersion and the dissolution of a system. Sometimes, capsule or compact dissolution could not be predicted by precipitation or powder dissolution due to plug formation. In this case, properly designed dosage forms were needed to break up this plug to optimize the dissolution profiles. On the contrary, formulations and dissolution conditions would have minimal effects on the dissolution profiles of a fast-dissolving solid dispersion. CONCLUSIONS: Different techniques are available to select the right polymers to optimize dissolution behaviors. However, it is important to understand the merits and limitations of each technique in order to optimize the formulations for amorphous solid dispersions.
Subject(s)
Chemistry, Pharmaceutical/methods , Technology, Pharmaceutical/methods , Capsules/chemistry , Cellulose/chemistry , Hot Temperature , Polymers/chemistry , Polymethacrylic Acids/chemistry , Povidone/chemistry , Powders/chemistry , SolubilityABSTRACT
Solid state manipulation by amorphous solid dispersion has been the subject of intensive research for decades due to their excellent potential for dissolution and bioavailability enhancement. The present review aims to highlight the latest advancement in this area, with focus on the fundamentals, characterization, formulation development and manufacturing of amorphous solid dispersions as well as the new generation amorphization technologies. Additionally, specific applications of amorphous solid dispersion in the formulation of herbal drugs or bioactive natural products are reviewed to reflect the growing interest in this relatively neglected area.
Subject(s)
Drug Carriers/chemistry , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/chemistry , Plant Preparations/administration & dosage , Plant Preparations/chemistry , Biological Availability , Chemistry, Pharmaceutical , Chemistry, Physical , Drug Stability , Particle Size , Pharmaceutical Preparations/metabolism , Plant Preparations/pharmacokinetics , Solubility , Solutions , ThermodynamicsABSTRACT
"New formulation and manufacturing methods are now available to efficiently and effectively increase solubility and maintain the supersaturation of a thermodynamically metastable state".
