Hot melt extrusion (HME) for amorphous solid dispersions: Predictive tools for processing and impact of drug–polymer interactions on supersaturation

Sarode, Ashish L.; Sandhu, Harpreet; Shah, Navnit; Malick, Waseem; Zia, Hossein

doi:10.1016/j.ejps.2012.12.012

Cited by 209 publications

(120 citation statements)

References 40 publications

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“…Statistical analysis results of these dissolution time points are summarized in Table IV. As expected, the polymer type had a significant impact on dissolution, which is mainly related to differences in polymer chemistry and interaction potential between drug substance and polymer (33,35). At early dissolution time points (<40 min), PVP VA64-containing dispersion and tablets showed higher drug release, whereas at later time points (>40 min), HPMCAScontaining dispersion and HME tablets showed higher release due to better maintenance of supersaturation.…”

Section: Hme Tablet Dissolution-statistical Analysissupporting

confidence: 51%

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

et al. 2016

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ABSTRACT. The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus-and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.

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Section: Hme Tablet Dissolution-statistical Analysissupporting

confidence: 51%

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

et al. 2016

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“…Eudragit EPO and Soluplus have been widely reported for the preparation of HME solid dispersions for enhancing the dissolution of poorly soluble drugs [28][29][30][31]. Although both polymers on their own are HME extrudable, neither of them were FDM printable even with the addition of drug.…”

Section: Processability Of Polymer Blend Based Solid Dispersions By Fdmmentioning

confidence: 99%

An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing

Alhijjaj

Belton

2016

European Journal of Pharmaceutics and Biopharmaceutics

230

134

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FDM 3D printing has been recently attracted increasing research efforts towards the production of personalized solid oral formulations. However, commercially available FDM printers are extremely limited with regards to the materials that can be processed to few types of thermoplastic polymers, which often may not be pharmaceutically approved materials nor ideal for optimizing dosage form performance of poor soluble compounds. This study explored the use of polymer blends as a formulation strategy to overcome this processability issue and to provide adjustable drug release rates from the printed dispersions. Solid dispersions of felodipine, the model drug, were successfully fabricated using FDM 3D printing with polymer blends of PEG, PEO and Tween 80 with either Eudragit E PO or Soluplus. As PVA is one of most widely used polymers in FDM 3D printing, a PVA based solid dispersion was used as a benchmark to compare the polymer blend systems to in terms processability. The polymer blends exhibited excellent printability and were suitable for processing using a commercially available FDM 3D printer. With 10% drug loading, all characterization data indicated that the model drug was molecularly dispersed in the matrices.During in vitro dissolution testing, it was clear that the disintegration behavior of the formulations significantly influenced the rates of drug release. Eudragit EPO based blend dispersions showed bulk disintegration; whereas the Soluplus based blends showed the 'peeling' style disintegration of strip-by-strip. The results indicated that interplay of the miscibility between excipients in the blends, the solubility of the materials in the dissolution media and the degree of fusion between the printed strips during FDM process can be used to manipulate the drug release rate of the dispersions. This brings new insight into the design principles of controlled release formulations using FDM 3D printing.

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“…Identifying suitable extrusion parameters is highly formulation dependent (41). The physicochemical properties of the API must be considered including the glass transition and melting temperatures, the degradation temperature, and the miscibility or solubility of the API in the polymer carrier (42)(43)(44).…”

Section: Extrusion-processing Windows Of Common Polymer Carriersmentioning

confidence: 99%

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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Abstract. Thermal processing of amorphous solid dispersions continues to gain interest in the pharmaceutical industry, as evident by several recently approved commercial products. Still, a number of pharmaceutical polymer carriers exhibit thermal or viscoelastic limitations in thermal processing, especially at smaller scales. Additionally, active pharmaceutical ingredients with high melting points and/or that are thermally labile present their own specific challenges. This review will outline a number of formulation and process-driven strategies to enable thermal processing of challenging compositions. These include the use of traditional plasticizers and surfactants, temporary plasticizers utilizing sub-or supercritical carbon dioxide, designer polymers tailored for hot-melt extrusion processing, and KinetiSol® Dispersing technology. Recent case studies of each strategy will be described along with potential benefits and limitations.

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Hot melt extrusion (HME) for amorphous solid dispersions: Predictive tools for processing and impact of drug–polymer interactions on supersaturation

Cited by 209 publications

References 40 publications

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

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