Stable amorphous solid dispersions of fenofibrate using hot melt extrusion technology: Effect of formulation and process parameters for a low glass transition temperature drug

Kallakunta, Venkata Raman; Sarabu, Sandeep; Bandari, Suresh; Batra, Amol; Bi, Vivian; Dürig, Thomas; Repka, Michael A.

doi:10.1016/j.jddst.2019.101395

Cited by 40 publications

(21 citation statements)

References 39 publications

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“…In order to potentially enhance the dissolution performance of HPMCAS-based ASDs, suitable surfactants might be added. It was shown that surfactants such as sodium lauryl sulfate or different types of poloxamer were able to improve the dissolution properties of HPMCAS-based ASDs ( 43 , 44 ).…”

Section: Resultsmentioning

confidence: 99%

Influence of Particle Size and Drug Load on Amorphous Solid Dispersions Containing pH-Dependent Soluble Polymers and the Weak Base Ketoconazole

2021

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Among the great number of poorly soluble drugs in pharmaceutical development, most of them are weak bases. Typically, they readily dissolve in an acidic environment but are prone to precipitation at elevated pH. This was aimed to be counteracted by the preparation of amorphous solid dispersions (ASDs) using the pH-dependent soluble polymers methacrylic acid ethylacrylate copolymer (Eudragit L100–55) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) via hot-melt extrusion. The hot-melt extruded ASDs were of amorphous nature and single phased with the presence of specific interactions between drug and polymer as revealed by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). The ASDs were milled and classified into six particle size fractions. We investigated the influence of particle size, drug load, and polymer type on the dissolution performance. The best dissolution performance was achieved for the ASD made from Eudragit L100–55 at a drug load of 10%, whereby the dissolution rate was inversely proportional to the particle size. Within a pH-shift dissolution experiment (from pH 1 to pH 6.8), amorphous-amorphous phase separation occurred as a result of exposure to acidic medium which caused markedly reduced dissolution rates at subsequent higher pH values. Phase separation could be prevented by using enteric capsules (Vcaps Enteric®), which provided optimal dissolution profiles for the Eudragit L100–55 ASD at a drug load of 10%.

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Section: Resultsmentioning

confidence: 99%

Influence of Particle Size and Drug Load on Amorphous Solid Dispersions Containing pH-Dependent Soluble Polymers and the Weak Base Ketoconazole

2021

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“…Like HMPC, HPMCAS also has a reasonably high Tg (Table II), which can aid in physical stability. Nevertheless, there are very few reports claiming high Tg of HPMCAS as the sole reason for stability (148). Part of the reason can be attributed to the fact that unlike HPMC, the promiscuous ability of HPMCAS to form intermolecular interactions always confound in many HPMCAS-based solid dispersions as a stability mechanism.…”

Section: Hydroxy Propyl Methyl Cellulose Acetate Succinate (Hpmcas)mentioning

confidence: 99%

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

et al. 2020

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Solid dispersion is the preferred technology to prepare efficacious forms of BCS class-II/IV APIs. To prepare solid dispersions, there exist a wide variety of polymeric carriers with interesting physicochemical and thermochemical characteristics available at the disposal of a formulation scientist. Since the advent of the solid dispersion technology in the early 1960s, there have been more than 5000 scientific papers published in the subject area. This review discusses the polymeric carrier properties of most extensively used polymers PVP, Copovidone, PEG, HPMC, HPMCAS, and Soluplus® in the solid dispersion technology. The literature trends about preparation techniques, dissolution, and stability improvement are analyzed from the Scopus® database to enable a formulator to make an informed choice of polymeric carrier. The stability and extent of dissolution improvement are largely dependent upon the type of polymeric carrier employed to formulate solid dispersions. With the increasing acceptance of transfer dissolution setup in the research community, it is required to evaluate the crystallization/precipitation inhibition potential of polymers under dynamic pH shift conditions. Further, there is a need to develop a regulatory framework which provides definition and complete classification along with necessarily recommended studies to characterize and evaluate solid dispersions.

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“…Furthermore, dissolution studies revealed an enhanced bioavailability rate of the ASD compared to the pure drug, and was almost equal to the market product [ 80 ]. Similarly, optimal amorphous extrudates of fenofibrate with three different grades of HPMCAS were developed and no recrystallization occurred after 45 days at accelerated conditions [ 102 ]. A recent study, in order to overcome the limitation of the high temperature required for the extrusion of HPMCAS [ 81 ], suggested different surfactants, such as poloxamer 188, poloxamer 407, and d-alpha tocopheryl polyethylene glycol 1000 succinate, to act as plasticizers and facilitate the process.…”

Section: Polyelectrolytes In Hot-melt Extrusionmentioning

confidence: 99%

Polyelectrolyte Matrices in the Modulation of Intermolecular Electrostatic Interactions for Amorphous Solid Dispersions: A Comprehensive Review

2021

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Polyelectrolyte polymers have been widely used in the pharmaceutical field as excipients to facilitate various drug delivery systems. Polyelectrolytes have been used to modulate the electrostatic environment and enhance favorable interactions between the drug and the polymer in amorphous solid dispersions (ASDs) prepared mainly by hot-melt extrusion. Polyelectrolytes have been used alone, or in combination with nonionic polymers as interpolyelectrolyte complexes, or after the addition of small molecular additives. They were found to enhance physical stability by favoring stabilizing intermolecular interactions, as well as to exert an antiplasticizing effect. Moreover, they not only enhance drug dissolution, but they have also been used for maintaining supersaturation, especially in the case of weakly basic drugs that tend to precipitate in the intestine. Additional uses include controlled and/or targeted drug release with enhanced physical stability and ease of preparation via novel continuous processes. Polyelectrolyte matrices, used along with scalable manufacturing methods in accordance with green chemistry principles, emerge as an attractive viable alternative for the preparation of ASDs with improved physical stability and biopharmaceutic performance.

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Stable amorphous solid dispersions of fenofibrate using hot melt extrusion technology: Effect of formulation and process parameters for a low glass transition temperature drug

Cited by 40 publications

References 39 publications

Influence of Particle Size and Drug Load on Amorphous Solid Dispersions Containing pH-Dependent Soluble Polymers and the Weak Base Ketoconazole

Influence of Particle Size and Drug Load on Amorphous Solid Dispersions Containing pH-Dependent Soluble Polymers and the Weak Base Ketoconazole

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

Polyelectrolyte Matrices in the Modulation of Intermolecular Electrostatic Interactions for Amorphous Solid Dispersions: A Comprehensive Review

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