Applicability of an Experimental Grade of Hydroxypropyl Methylcellulose Acetate Succinate as a Carrier for Formation of Solid Dispersion with Indomethacin

Ueda, Hiroshi; Hirakawa, Yuya; Tanaka, Hironori; Miyano, Tetsuya; Sugita, Katsuji

doi:10.3390/pharmaceutics13030353

Cited by 11 publications

(10 citation statements)

References 36 publications

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“…[9] Converting crystalline drugs into an amorphous state by disseverance of the crystal lattice may prove a vital approach to enhance drug solubility as it is in the higher energy state. [10,11,12] Nowadays, Solid dispersion (SD) emerged as a novel technique for delivery of drugs to overcome the barriers to drug absorption. In this technique, one or more active ingredients dispersed in a hydrophilic carrier/polymer in a solid-state which can be prepared by various methods i.e.…”

Section: Introductionmentioning

confidence: 99%

Design and Development of Fenofibrate Solid Dispersions for Solubility Enhancement

2022

pnr

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This research work designed to overcome the problems associated with poorly aqueous soluble drug. Fenofibrate (FENO) being BCS Class II drug shows low solubility but permeability is high. Compatibility of the drug and polymer studies was done by FTIR. Physical mixtures (PM) of the drug and polymer HPMCAS were prepared by trituration method. Fenofibrate solid dispersions (SD) were prepared by common solvent technique ascribed feasibility in laboratory scale. Physical state of formulations was characterized by powder XRD, TGA. Solubility of pure drug (FENO), Physical mixture and SD found to be 0.3, 0.78±0.15 to 1.15±0.28 and 2.17±0.37 to 3.25±0.14 mg/ml respectively. Percentage yield and percentage drug content were determined and found within satisfactory range. The maximum cumulative percentage of drug release from pure drug (FENO), Physical mixture and SD found to be 34.5%, 72.1 and 97.2% respectively at 60 minutes. Microscopy (SEM) study was found that the prepared solid dispersion has porous morphology. The present study establishes the increased bioavailability of the optimized batch when compared with the pure FENO. There was significant (50%) increase in absorption of Fenofibrate observed from the in vitro everted gut sac model. SD of FENO was developed successfully. The solubility of FENO was ameliorated significantly while compared with API (pure FENO). This research work found formulation of SD preferable technique to enhance solubility and enhance dissolution of lipophilic drugs.

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Section: Introductionmentioning

confidence: 99%

Design and Development of Fenofibrate Solid Dispersions for Solubility Enhancement

2022

pnr

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“…Since it has been reported that the deviation in Tgs values obtained experimentally from the theoretical values indicates the presence of intermolecular interactions between the components [ 35 , 49 ], it was considered that AntiY 5 R and NaTC interacted with each other even in the amorphous state. Furthermore, it has also been reported that the increase in Tg and intermolecular interactions with polymers could inhibit the crystallization of drugs and stabilize an amorphous state during storage in several PASD preparations [ 45 , 51 , 52 ]. Therefore, the co-amorphous system of AntiY 5 R with NaTC would be quite stable, and the amorphous state might be maintained even under accelerated conditions at 40 °C.…”

Section: Resultsmentioning

confidence: 99%

Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature

et al. 2022

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Brick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures (Tg) are relatively lower than those of polymeric amorphous solid dispersions, suggesting the instability of the co-amorphous system. This study aimed to formulate a stable co-amorphous system for brick dust molecules by utilizing sodium taurocholate (NaTC) with a higher Tg. A novel neuropeptide Y5 receptor antagonist (AntiY5R) and NaTC with Tg of 155 °C were used as the brick dust model and coformer, respectively. Ball milling formed a co-amorphous system for AntiY5R and NaTC (AntiY5R-NaTC) at various molar ratios. Deviation from the theoretical Tg value and peak shifts in Fourier-transform infrared spectroscopy indicated intermolecular interactions between AntiY5R and NaTC. AntiY5R-NaTC at equal molar ratios resulting in an 8.5-fold increase in AntiY5R solubility over its crystalline form. The co-amorphous system remained amorphous for 1 month at 25 °C and 40 °C. These results suggest that the co-amorphous system formed by utilizing NaTC as a coformer could stably maintain the amorphous state and enhance the solubility of brick dust molecules.

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“…Indomethacin was purchased from Kongo Chemical Co., Ltd. (Toyama, Japan). A commercial grade of HPMCAS “Shin-Etsu AQOAT® type MG” and an experimental grade “type MX” originally developed were kindly gifted by Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan) [ 19 ]. GIT-0 lipid (20 wt.% phospholipid dissolved into dodecane), Prisma HT buffer (pH 6.5), and acceptor sink buffer (ASB) were purchased from pION Inc. (MA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Hence, designing and developing a novel solid dispersion carrier with lower T g is desirable. In a previous study, we focused on an experimental grade of HPMCAS originally designed with lower T g than commercial grade [ 19 ]. Physicochemical investigation of its solid dispersion revealed the formation of intermolecular interaction with indomethacin (IMC) inhibited crystallization.…”

Section: Introductionmentioning

confidence: 99%

Dissolution-permeation of hot-melt extruded amorphous solid dispersion comprising an experimental grade of HPMCAS

Tanaka¹,

Miyano²,

Ueda³

2023

ADMET DMPK

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Background and purpose: Physicochemical properties of an amorphous solid dispersion (ASD) comprising an experimental grade of hydroxypropyl methylcellulose acetate succinate (HPMCAS-MX) with lower glass transition temperature have been previously investigated. This study aimed to evaluate applicability of HPMCAS-MX to hot-melt extrusion (HME) and dissolution-permeation performance of prepared ASDs using MicroFLUX. Review approach: A physical mixture of indomethacin (IMC) and HPMCAS-MX or -MG (a commercial grade with higher transition temperature) at 20:80 weight ratio was hot-melt extruded to prepare an ASD (IMC-MX and IMC-MG, respectively). The dissolution-permeation performance and the stability of the ASDs were measured. Key results: A torque reduction at 120 °C implied that IMC-MX transformed into an amorphous state at this temperature, but IMC-MG required around 170 °C. This result was supported by Raman mapping of the the HME samples. IMC-MG and IMC-MX remained in an amorphous state at 40 °C for three months. The initial dissolution rate and solubility of the ASDs were higher than that of crystalline IMC. The apparent permeability of IMC from IMC-MX and IMC-MG was comparable but was approximately two-fold higher than that from crystalline IMC. Conclusion: HPMCAS-MX enabled HME process at a lower temperature and improved the dissolution-permeation performance of indomethacin.

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Applicability of an Experimental Grade of Hydroxypropyl Methylcellulose Acetate Succinate as a Carrier for Formation of Solid Dispersion with Indomethacin

Cited by 11 publications

References 36 publications

Design and Development of Fenofibrate Solid Dispersions for Solubility Enhancement

Design and Development of Fenofibrate Solid Dispersions for Solubility Enhancement

Formation of a Stable Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate with High Glass Transition Temperature

Dissolution-permeation of hot-melt extruded amorphous solid dispersion comprising an experimental grade of HPMCAS

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