Abstract
The effect of cooling on the degree of crystallinity, solid-state and dissolution properties of multi-component hot-melt extruded solid dispersions [SD] is of great interest for the successful formulation of amorphous SDs and is an area that is unreported, especially in the context of improving the stability of these specific systems. The thermal solid-state properties, degree of crystallinity, drug–polymer interactions, solubility and physical stability over time were investigated. X-ray powder diffraction [XRPD] and hyper differential scanning calorimetry [DSC] confirmed that indomethacin [INM] was converted to the amorphous state; however, the addition of poloxamer 407 [P407] had a significant effect on the degree of crystallinity and the solubility of the SD formulations. Spectroscopy studies identified the mechanism of interaction and solubility studies, showing a higher dissolution rate compared to amorphous and pure INM in pH 1.2 with a kinetic solubility of 20.63 µg/mL and 34.7 µg/mL after 3 and 24 h. XRPD confirmed that INM remained amorphous after 5 months stability testing in solid solutions with Poly(vinylpyrrolidone-co-vinyl acetate) [PVP VA64] and Plasdone S-630 [PL-S630]. Although cooling had a significant effect on the degree of crystallinity and on solubility of INM, the cooling method used did not have any significant effect on the amorphous stability of INM over time.
Highlights
Within both the pharmaceutical industry and academia, there is a strong interest in utilizing hot melt extrusion [HME] to prepare amorphous solid dispersions [SDs] which have the potential to significantly improve the kinetic solubility and the bioavailability of BCS class II drugs which have poor aqueous solubility and high permeability [1]
To investigate the crystallization tendency of the API, a selected SD formulation was air cooled [AC] to 25 ◦C by an air pipe connector attached to the 2 mm die of the extruder, cooled to normal room temperature (25 ◦C) [NT], the same as air cooling except with no air pipe connector and quench cooled using liquid nitrogen, [Liq N2], to examine the effect of slow and rapid cooling processes on the amorphous stability and solubility of INM
The HSPs developed by Van Krevelen and Hoftyzer group were used as a substitute for the Flory–Huggins theory to explore the nature of interactions that occur within drug–polymer systems and is mainly based upon the chemical structures of each of the pure components
Summary
Within both the pharmaceutical industry and academia, there is a strong interest in utilizing hot melt extrusion [HME] to prepare amorphous solid dispersions [SDs] which have the potential to significantly improve the kinetic solubility and the bioavailability of BCS class II drugs which have poor aqueous solubility and high permeability [1]. Very little has been reported on how various cooling methods effect the degree of crystallinity, solid state properties and dissolution rate of multi-component amorphous SDs. INM has been used as a model drug in this study which is a BCS class II API (low solubility, high permeability). The relationship between cooling and the physicochemical/dissolution properties of the drug and polymeric carriers is an area that is very important in the manufacture and development of SDs. It is reported in the literature that slow cooling enhances the physical stability of amorphous INM [11]; Meng et al (2015) stated that the faster the cooling rate, the lower the crystallinity of the API [12]. Since this study uses a semi-crystalline plasticizer to improve the solubility of INM, the degree of crystallinity of the semi-crystalline polymer in the SD formulations must be examined as it can affect the processing and physical properties of the API
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
