Investigation of Polymer-Surfactant and Polymer-Drug-Surfactant Miscibility for Solid Dispersion

Abstract

In a solid dispersion (SD), the drug is generally dispersed either molecularly or in the amorphous state in polymeric carriers, and the addition of a surfactant is often important to ensure drug release from such a system. The objective of this investigation was to screen systematically polymer-surfactant and polymer-drug-surfactant miscibility by using the film casting method. Miscibility of the crystalline solid surfactant, poloxamer 188, with two commonly used amorphous polymeric carriers, Soluplus® and HPMCAS, was first studied. Then, polymer-drug-surfactant miscibility was determined using itraconazole as the model drug, and ternary phase diagrams were constructed. The casted films were examined by DSC, PXRD and polarized light microscopy for any crystallization or phase separation of surfactant, drug or both in freshly prepared films and after exposure to 40°C/75% RH for 7, 14, and 30 days. The miscibility of poloxamer 188 with Soluplus® was <10% w/w, while its miscibility with HPMCAS was at least 30% w/w. Although itraconazole by itself was miscible with Soluplus® up to 40% w/w, the presence of poloxamer drastically reduced its miscibility to <10%. In contrast, poloxamer 188 had minimal impact on HPMCAS-itraconazole miscibility. For example, the phase diagram showed amorphous miscibility of HPMCAS, itraconazole, and poloxamer 188 at 54, 23, and 23% w/w, respectively, even after exposure to 40°C/75% RH for 1 month. Thus, a relatively simple and practical method of screening miscibility of different components and ultimately physical stability of SD is provided. The results also identify the HPMCAS-poloxamer 188 mixture as an optimal surface-active carrier system for SD.

Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability

“…The drug-polymer, polymer-polymer, and drug-polymerpolymer miscibility testing was performed by the film-casting method described previously. 41,46 For this purpose, 500 mg of each haloperidol-Kollidon ® VA64 (1:9, 2:8 and 3:7), haloperidol-Affinisol ™ 15 cP (1:9, 2:8 and 3:7), Kollidon ® VA64-Affinisol ™ 15 cP (1:1) binary mixtures, and haloperidol-Kollidon ® VA64-Affinisol ™ 15 cP ternary mixtures (1:5:5 and 2:5:5) were dissolved in 3 mL of methanol-dichloromethane (1:1) mixture and shaken for 1 h in a closed scintillation vial using wrist action shaker. One milliliter of each solution was then poured on a glass plate, and the 200microns film was casted using a film applicator.…”

“…It was also important to establish that the 2 polymers are miscible with each other. A film-casting method previously developed in our laboratory 41,46 was used to evaluate drug-polymer, polymer-polymer, and drug-polymer-polymer miscibility, and the results are presented below:…”

“…However, unless the miscibility of the drug with the polymer used is established, the drug may crystallize out in tablets during shelf life, resulting in physical stability issues and variability in drug release. 41 For successful preparation of 3D printed tablets containing ASD by FDM, polymers have to be pharmaceutical grade, the drug should be miscible with the polymer, the extruded filaments should be flexible to be used in the FDM 3D printer, and the printing should not require very high temperature. Moreover, it is preferable that the tablets should release drugs as fast as possible and the amounts of nonmelting fillers used to enhance drug release should be avoided or reduced.…”

Analytical and Computational Methods for the Estimation of Drug-Polymer Solubility and Miscibility in Solid Dispersions Development

“…Janssens et al [65] have analyzed the miscibility in ternary systems of itraconazole with polyethylene glycol (PEG) and HPMC polymer blends, of different molecular weights, using M-DSC and XRPD. Miscibility in ternary polymer-drug-surfactant systems hydroxypropylmethylcellulose acetate succinate (HPMCAS)-itraconazole-Soluplus ® has been also analyzed using DSC, XRPD, and PLM [66]. Parikh et al [67] have proposed the preparation of the film-casted samples to investigate miscibility of the drug and the polymer using techniques, such as DSC, XRPD, and PLM.…”

Preparation and Evaluation of Dolutegravir Solid Dispersions

“…According to the Biopharmaceutical Classification Scheme, dolutegravir is considered as class II drug, i.e., water insoluble, lipophilic and highly permeable compound. Therefore, it is possible to improve its bioavailability by increasing apparent solubility in water through solid dispersion technology [5,6]. The bioavailability of dolutegravir is approximately 34%.…”