Hydroxypropyl cellulose stabilizes amorphous solid dispersions of the poorly water soluble drug felodipine

Sarode, Ashish L.; Malekar, Swapnil A.; Cote, Catherine; Worthen, David R.

doi:10.1016/j.carbpol.2014.06.039

Cited by 52 publications

(33 citation statements)

References 23 publications

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“…Solid dispersions are widely used formulations for improving the dissolution of poorly water-soluble drugs [14,15]. Molecular dispersions in which the crystalline drug is dispersed in the polymeric matrices on a molecular scale have been recognized as being highly effective for improving the dissolution and subsequent bioavailability of many poorly soluble drugs [16,17]. This study used a BCS class II drug [18], felodipine, as a model poorly soluble drug to develop FDM 3D printable blends made of pharmaceutically approved excipients.…”

Section: Introductionmentioning

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

237

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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Section: Introductionmentioning

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

237

134

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“…Pharmaceutical HME is currently being investigated by both industry and academia as a means to increase the release rate of poorly water-soluble APIs by melt-mixing them with hydrophilic, water-soluble polymers (Repka, Langley, & DiNunzio, 2013). HME can help overcome poor API bioavailability, create new modified-release drug systems, and mask bitter tastes (Sarode, Malekar, Cote, & Worthen, 2014). At the same time, an increasing body of literature exists on the production of controlled release dosages by melt-mixing readily water-soluble APIs with rate-controlling polymers.…”

Section: Introductionmentioning

confidence: 99%

Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: Structure and drug release correlation

Zhang

Yang

et al. 2017

Carbohydrate Polymers

173

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The objective of this study was to develop a new approach for fabrication of zero order release of active pharmaceutical ingredients (APIs) using hot-melt extrusion (HME) and 3D printing technology to generate tablets with specific 3D structures. By correlating the geometry of the 3D printed tablets with their dissolution and drug release rates, mathematical models that have been developed to describe drug release mechanisms were also studied. Acetaminophen was used as a model drug, and Benecel™ hydroxypropyl methylcellulose (HPMC) E5 and Soluplus® were used to formulate nine fuse depositional 3D-printed tablets with different inner core fill densities and outside shell thicknesses. This work reports the successful fabrication of solid-dispersion filaments with an API dispersed in HPMC based matrix via HME technology, and the production of zero order controlled release tablets with different 3D structures (tablets #3, 5, 6, and 9) using a 3D printer.

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“…The solubility and stability of montelukast sodium in the oral solution were two important factors. Soluplus [26,27], Kolliphor [28], PVP [29,30] and HP-b-CD [31,32] were used as solubilizers in this study, and have been extensively used in pharmaceutical oral products. Montelukast sodium had an aqueous solubility of about 2 mg/ ml, indicating that it was slightly soluble in water [9,10].…”

Section: Resultsmentioning

confidence: 99%

Novel montelukast sodium-loaded clear oral solution prepared with hydroxypropyl-β-cyclodextrin as a solubilizer and stabilizer: enhanced stability and bioequivalence to commercial granules in rats

Kim

Kwon

et al. 2015

J Incl Phenom Macrocycl Chem

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To develop a montelukast sodium-loaded clear oral solution with enhanced stability that was bioequivalent to commercial granules in rats for the treatment of asthma, various montelukast sodium-loaded solutions were prepared with various amounts of solubilizers and stabilizer, and their solubility and stability were investigated. Furthermore, the dissolution and pharmacokinetic studies were carried out in rats with the optimised formulation and the commercial montelukast sodium-loaded granules. Among the solubilizers tested in this study, hydroxypropyl-b-cyclodextrin (HP-b-CD) was selected because it greatly improved the drug solubility and stability. Furthermore, EDTA sodium was used as a stabilizer because it gave excellent stability. In particular, the montelukast-loaded oral solution, an aqueous clear solution containing montelukast sodium, HP-b-CD, methylparaben sodium, propylparaben sodium and EDTA sodium at w/v percentages of 1.04/156/1.8/0.2/1, gave similar dissolution to the commercial granules in 0.5 % (w/v) sodium lauryl sulphate in water, FDA-regulated dissolution medium. This oral solution gave similar plasma concentrations and pharmacokinetic parameters to the commercial granules, suggesting that it was bioequivalent to the commercial granules in rats. Moreover, it was physically and chemically stable at 25°C/60 % RH and 40°C/75 % RH for at least 12 months. Thus, this oral solution is strongly recommended as an alternative to the oral montelukast-loaded product for the treatment of asthma.

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Hydroxypropyl cellulose stabilizes amorphous solid dispersions of the poorly water soluble drug felodipine

Cited by 52 publications

References 23 publications

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

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

Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: Structure and drug release correlation

Novel montelukast sodium-loaded clear oral solution prepared with hydroxypropyl-β-cyclodextrin as a solubilizer and stabilizer: enhanced stability and bioequivalence to commercial granules in rats

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