CHAN SIOK YEE (DR.)'s Journal | 6. Publication and Oral presentation by Chan Siok Yee (Sam)

Solution-mediated transformation has been cited as one of the main problems that deteriorate dissolution performances of solid dispersion (SD). This is mainly attributed by the recrystallization tendency of poorly soluble drug. Eventually, it will lead to extensive agglomeration which is a key process in reducing the dissolution performance of SD and offsets the true benefit of SD system. Here, a post-processing treatment is suggested in order to reduce the recrystallization tendency and hence bring forth the dissolution advantage of SD system.

While hot melt extrusion is now established within the pharmaceutical industry, the prediction of miscibility, processability and structural stability remains a pertinent issue, including the issue of whether molecular interaction is necessary for suitable performance. Here we integrate the use of theoretical and experimental drug–polymer interaction assessment with determination of processability and structure of dispersions in two polyvinylpyrrolidone-based polymers (PVP and PVP vinyl acetate, PVPVA). Caffeine and paracetamol were chosen as model drugs on the basis of their differing hydrogen bonding potential with PVP. Solubility parameter and interaction parameter calculations predicted a greater miscibility for paracetamol, while ATR-FTIR confirmed the hydrogen bonding propensity of the paracetamol with both polymers, with little interaction detected for caffeine. PVP was found to exhibit greater interaction and miscibility with paracetamol than did PVPVA. It was noted that lower processing temperatures (circa 40 C below the Tg of the polymer alone and Tm of the crystalline drug) and higher drug loadings with associated molecular dispersion up to 50% w/w were possible for the paracetamol dispersions, although molecular dispersion with the non-interactive caffeine was noted at loadings up to 20% w./w. A lower processing temperature was also noted for caffeine-loaded systems despite the absence of detectable interactions. The study has therefore indicated that theoretical and experimental detection of miscibility and drug–polymer interactions may lead to insights into product processing and extrudate structure, with direct molecular interaction representing a helpful but not essential aspect of drug–polymer combination prediction.

Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API. However, there are inconsistent dissolution performances of solid dispersion reported which entails further investigation. In this study, solid dispersions of Ketoprofen in three hydrophilic carriers, i.e. PVP K30, PVPVA 6:4 and PVA were prepared and characterized. Physical characterization of the physical mixture of Ketoprofen and carriers shows certain extent of amorphization of the API. This result is coinciding to evaluation of drugepolymer interaction using ATR-FTIR whereby higher amorphization was seen in samples with higher drugepolymer interaction. XRPD scanning confirms that fully amorphous solid dispersion was obtained for SD KTP PVP K30 and PVPVA system whereas partially crystalline system was obtained for SD KTP PVA. Interestingly, dissolution profiles of the solid dispersion had shown that degree of amorphization of KTP was not directly proportional to the dissolution rate enhancement of the solid dispersion system. Thus, it is concluded that complete amorphization does not guarantee dissolution enhancement of an amorphous solid dispersion system.

Bioavailability of a BCS class II substance can be highly affected by its formulation design. In this respect, solid dispersion in a hydrophilic carrier formulation was introduced a decade ago to resolve the problem of BCS class II substance. With that, several processing methods of the solid dispersion have been studied. Amongst the advent processing methods hot melt extrusion (HME) has appeared as a robust manufacturing method in formulating solid dispersion. The use of this method offers many advantages as compared to the other conventional methods such as environmental friendly, cost sparing and readily scalable. This review explores the use of hot melt extrusion in the preparation of solid dispersion. Besides, current trend of the investigated active pharmaceutical ingredient (API) and the recommended carrier used in this manufacturing process were summarized and categorized. Other concerns regarding the use various excipients and additives were also investigated and grouped into easily accessible format such as table. Alongside to the review, results drawn from the literature regarding the performance of the obtained HME based solid dispersion were also discussed.