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Formulation and Characterization of Solid Dispersion Prepared by Hot Melt Mixing: A Fast Screening Approach for Polymer Selection.

Enose AA, Dasan PK, Sivaramakrishnan H, Shah SM - J Pharm (Cairo) (2014)

Bottom Line: Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability.Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymer-plasticizer-sulindac combinations.The formulations were characterized by advanced techniques like optical microscopy, differential scanning calorimetry, hot stage microscopy, dynamic vapor sorption, and X-ray diffraction.

View Article: PubMed Central - PubMed

Affiliation: Piramal Enterprise Limited, 1 Nirlon Knowledge Park, Goregaon East, Mumbai, Maharashtra 400063, India.

ABSTRACT
Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymer-plasticizer-sulindac combinations. The sulindac-polymer-plasticizer combination that was stable with good film forming properties was processed by hot melt mixing, a technique close to hot melt extrusion, to predict its behavior in a hot melt extrusion process. Hot melt mixing is not a substitute to hot melt extrusion but is an aid in predicting the formation of molecularly dispersed form of a given set of drug-polymer-plasticizer combination in a hot melt extrusion process. The formulations were characterized by advanced techniques like optical microscopy, differential scanning calorimetry, hot stage microscopy, dynamic vapor sorption, and X-ray diffraction. Subsequently, the best drug-polymer-plasticizer combination obtained by hot melt mixing was subjected to hot melt extrusion process to validate the usefulness of hot melt mixing as a predictive tool in hot melt extrusion process.

No MeSH data available.


Hot stage microscopy study of formulations described in Table 2 ((A) to (F)) and SUL (G). The images on the extreme left are the initial images of all samples tested. The middle and the right image are the images where thermal changes are observed, especially melting. (A) and (B) observed at a magnification of 10x, (C) observed at 20x, (D) observed at 10x, (E) and (F) observed at 20x, and (G) observed at 40x magnification in polarized light.
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fig4: Hot stage microscopy study of formulations described in Table 2 ((A) to (F)) and SUL (G). The images on the extreme left are the initial images of all samples tested. The middle and the right image are the images where thermal changes are observed, especially melting. (A) and (B) observed at a magnification of 10x, (C) observed at 20x, (D) observed at 10x, (E) and (F) observed at 20x, and (G) observed at 40x magnification in polarized light.

Mentions: The hot stage microscopy images are shown in Figure 4. SUL exhibited melting at 190.7°C (Figure 4(G)) which correlate well with the sharp endothermic transition observed at 188°C in DSC. No such thermal event was observed for formulations A to F between 185°C and 190°C. For Figure 4(A), with PEG1000 as the plasticizer, the thermal event started at 110°C whereas in Figure 4(B), with TEC as the plasticizer, the thermal event was shifted to 86°C. This behavior can be attributed to the glass transition temperature of PPP at 70°C. For Figures 4(C) and 4(D) containing HPC, with PEG1000 and TEC as the plasticizers, respectively, the melting initiated at 146°C and 162°C, respectively. For Figures 4(E) and 4(F) containing HPMC, with PEG1000 and TEC as the plasticizers, respectively, melting initiated at 243°C and 228°C, respectively. For SUL complete melting was observed in a span of 2°C after its initiation. For formulations of PPP, HPC, and HPMC there was a broad range of 20°C–30°C during which complete change of state was observed. Molecular dispersion of SUL in various polymers is confirmed as no specific thermal changes were observed at 188°C.


Formulation and Characterization of Solid Dispersion Prepared by Hot Melt Mixing: A Fast Screening Approach for Polymer Selection.

Enose AA, Dasan PK, Sivaramakrishnan H, Shah SM - J Pharm (Cairo) (2014)

Hot stage microscopy study of formulations described in Table 2 ((A) to (F)) and SUL (G). The images on the extreme left are the initial images of all samples tested. The middle and the right image are the images where thermal changes are observed, especially melting. (A) and (B) observed at a magnification of 10x, (C) observed at 20x, (D) observed at 10x, (E) and (F) observed at 20x, and (G) observed at 40x magnification in polarized light.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590819&req=5

fig4: Hot stage microscopy study of formulations described in Table 2 ((A) to (F)) and SUL (G). The images on the extreme left are the initial images of all samples tested. The middle and the right image are the images where thermal changes are observed, especially melting. (A) and (B) observed at a magnification of 10x, (C) observed at 20x, (D) observed at 10x, (E) and (F) observed at 20x, and (G) observed at 40x magnification in polarized light.
Mentions: The hot stage microscopy images are shown in Figure 4. SUL exhibited melting at 190.7°C (Figure 4(G)) which correlate well with the sharp endothermic transition observed at 188°C in DSC. No such thermal event was observed for formulations A to F between 185°C and 190°C. For Figure 4(A), with PEG1000 as the plasticizer, the thermal event started at 110°C whereas in Figure 4(B), with TEC as the plasticizer, the thermal event was shifted to 86°C. This behavior can be attributed to the glass transition temperature of PPP at 70°C. For Figures 4(C) and 4(D) containing HPC, with PEG1000 and TEC as the plasticizers, respectively, the melting initiated at 146°C and 162°C, respectively. For Figures 4(E) and 4(F) containing HPMC, with PEG1000 and TEC as the plasticizers, respectively, melting initiated at 243°C and 228°C, respectively. For SUL complete melting was observed in a span of 2°C after its initiation. For formulations of PPP, HPC, and HPMC there was a broad range of 20°C–30°C during which complete change of state was observed. Molecular dispersion of SUL in various polymers is confirmed as no specific thermal changes were observed at 188°C.

Bottom Line: Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability.Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymer-plasticizer-sulindac combinations.The formulations were characterized by advanced techniques like optical microscopy, differential scanning calorimetry, hot stage microscopy, dynamic vapor sorption, and X-ray diffraction.

View Article: PubMed Central - PubMed

Affiliation: Piramal Enterprise Limited, 1 Nirlon Knowledge Park, Goregaon East, Mumbai, Maharashtra 400063, India.

ABSTRACT
Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymer-plasticizer-sulindac combinations. The sulindac-polymer-plasticizer combination that was stable with good film forming properties was processed by hot melt mixing, a technique close to hot melt extrusion, to predict its behavior in a hot melt extrusion process. Hot melt mixing is not a substitute to hot melt extrusion but is an aid in predicting the formation of molecularly dispersed form of a given set of drug-polymer-plasticizer combination in a hot melt extrusion process. The formulations were characterized by advanced techniques like optical microscopy, differential scanning calorimetry, hot stage microscopy, dynamic vapor sorption, and X-ray diffraction. Subsequently, the best drug-polymer-plasticizer combination obtained by hot melt mixing was subjected to hot melt extrusion process to validate the usefulness of hot melt mixing as a predictive tool in hot melt extrusion process.

No MeSH data available.