Limits...
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.


Approach for screening and selection of polymer and its combination with plasticizer.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4590819&req=5

sch1: Approach for screening and selection of polymer and its combination with plasticizer.

Mentions: In the current investigation, a systematic approach is described that can be used for development of hot melt mix/extrudates of drugs with varying physical properties (Scheme 1). Many of the new chemical entities have good activity but lack good physicochemical properties. Low solubility, low absorption, and/or both are the major factors responsible for failure of a new chemical entity. The former issue of solubility can be taken care of by formulating molecularly dispersed drug in form of solid dispersion. In development of HME a very large quantity of drug is required which is a limitation in new drug discovery process. Here we propose a systematic approach for determining the right combination of drug-polymer-plasticizer using minimal quantity of drug. After initial film forming studies, a process (hot melt mixing) that tries to mimic the HME process was developed to formulate a solid solution of the drug in polymer. The amorphization of SUL was confirmed by optical microscopy, differential scanning calorimetry (DSC), X-ray diffraction, hot stage microscopy [18], and dynamic vapor sorption [6, 10, 11, 19–22]. The solid solution/dispersion was evaluated for drug content, purity, solid state stability by DSC, and increase in solubility at different pH (water, pH 1.2, pH 4.5, pH 6.8, and pH 7.4) [23]. The solubility of SUL was increased by many folds in all the media tested indicating better dissolution in the GIT. Finally the drug-polymer-plasticizer combination screened by film casting method and hot melt mixing was subjected to HME to confirm the usability of hot melt mixing as a tool for predicting behavior of drug-polymer-plasticizer combination in a HME process.


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)

Approach for screening and selection of polymer and its combination with plasticizer.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

sch1: Approach for screening and selection of polymer and its combination with plasticizer.
Mentions: In the current investigation, a systematic approach is described that can be used for development of hot melt mix/extrudates of drugs with varying physical properties (Scheme 1). Many of the new chemical entities have good activity but lack good physicochemical properties. Low solubility, low absorption, and/or both are the major factors responsible for failure of a new chemical entity. The former issue of solubility can be taken care of by formulating molecularly dispersed drug in form of solid dispersion. In development of HME a very large quantity of drug is required which is a limitation in new drug discovery process. Here we propose a systematic approach for determining the right combination of drug-polymer-plasticizer using minimal quantity of drug. After initial film forming studies, a process (hot melt mixing) that tries to mimic the HME process was developed to formulate a solid solution of the drug in polymer. The amorphization of SUL was confirmed by optical microscopy, differential scanning calorimetry (DSC), X-ray diffraction, hot stage microscopy [18], and dynamic vapor sorption [6, 10, 11, 19–22]. The solid solution/dispersion was evaluated for drug content, purity, solid state stability by DSC, and increase in solubility at different pH (water, pH 1.2, pH 4.5, pH 6.8, and pH 7.4) [23]. The solubility of SUL was increased by many folds in all the media tested indicating better dissolution in the GIT. Finally the drug-polymer-plasticizer combination screened by film casting method and hot melt mixing was subjected to HME to confirm the usability of hot melt mixing as a tool for predicting behavior of drug-polymer-plasticizer combination in a HME process.

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.