Congruent release of drug and polymer: A “sweet spot” in the dissolution of amorphous solid dispersions

Saboo, Sugandha; Mugheirbi, Naila A.; Zemlyanov, Dmitry; Kestur, Umesh S.; Taylor, Lynne S.

doi:10.1016/j.jconrel.2019.01.039

Cited by 120 publications

(132 citation statements)

References 40 publications

Supporting

Mentioning

123

Contrasting

Order By: Relevance

“…While pure HPMCAS solely tended to dissolve instead of swell, the situation profoundly changed for the ASDs containing CXB, which exhibited a high degree of swelling and a low degree of erosion. As reported by Han et al and Saboo et al this could be a result of incongruent release of polymer and drug from the ASD caused by water-induced phase separation [39,40]. The FT-IR spectra after buffer treatment indicated an AAPS of CXB and HPMCAS or at least revealed a weakening of the interactions between drug and polymer.…”

Section: Discussionmentioning

confidence: 56%

Impact of HPMCAS on the Dissolution Performance of Polyvinyl Alcohol Celecoxib Amorphous Solid Dispersions

Monschke

Wagner

2020

Pharmaceutics

View full text Add to dashboard Cite

Amorphous solid dispersions (ASDs) have been proven to increase the bioavailability of poorly soluble drugs. It is desirable that the ASD provide a rapid dissolution rate and a sufficient stabilization of the generated supersaturation. In many cases, one polymer alone is not able to provide both features, which raises a need for reasonable polymer combinations. In this study we aimed to generate a rapidly dissolving ASD using the hydrophilic polymer polyvinyl alcohol (PVA) combined with a suitable precipitation inhibitor. Initially, PVA and hydroxypropylmethylcellulose acetate succinate (HPMCAS) were screened for their precipitation inhibitory potential for celecoxib in solution. The generated supersaturation in presence of PVA or HPMCAS was further characterized using dynamic light scattering. Binary ASDs of either PVA or HPMCAS (at 10% and 20% drug load) were prepared by hot-melt extrusion and solid-state analytics were conducted using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and fourier-transformed infrared spectroscopy (FT-IR). The non-sink dissolution studies of the binary ASDs revealed a high dissolution rate for the PVA ASDs with subsequent precipitation and for the HPMCAS ASDs a suppressed dissolution. In order to utilize the unexploited potential of the binary ASDs, the PVA ASDs were combined with HPMCAS either predissolved or added as powder and also formulated as ternary ASD. We successfully generated a solid formulation consisting of the powdered PVA ASD and HPMCAS powder, which was superior in monophasic non-sink dissolution and biorelevant biphasic dissolution studies compared to the binary and ternary ASDs.

show abstract

Section: Discussionmentioning

confidence: 56%

Impact of HPMCAS on the Dissolution Performance of Polyvinyl Alcohol Celecoxib Amorphous Solid Dispersions

Monschke

Wagner

2020

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Sun and Lee do not report the formation of a drug-rich phase in the dissolution-controlled case. However, at least for certain formulations, the formation of colloidal states is possible for this dissolution scenario, as reported by Saboo et al (2019): the congruent release of polymer and API (dissolution controlled release) was proposed to be essential for the formation of particles by ALPS, which is in line with the concept of the dissolution controlled release.…”

Section: Dissolution Mechanismsmentioning

confidence: 54%

“…In literature, different examples of GLPS (Mosquera-Giraldo & Taylor, 2015;Mosquera-Giraldo et al, 2018b), and LLPS (Ilevbare & Taylor, 2013;Indulkar et al, 2016;Saboo et al, 2019) (together referred to as ALPS in this review) evolving during ASD dissolution were reported. As already pointed out in Section 4, from a physicochemical point of view, ALPS only occurs if supersaturated drug concentration exceeds the amorphous solubility (Taylor & Zhang, 2016;Baghel et al, 2018;Stewart et al, 2019).…”

Section: Api In Amorphous-liquid Phase Separationmentioning

confidence: 99%

Mechanisms of increased bioavailability through amorphous solid dispersions: a review

2019

View full text Add to dashboard Cite

Amorphous solid dispersions (ASDs) can increase the oral bioavailability of poorly soluble drugs. However, their use in drug development is comparably rare due to a lack of basic understanding of mechanisms governing drug liberation and absorption in vivo. Furthermore, the lack of a unified nomenclature hampers the interpretation and classification of research data. In this review, we therefore summarize and conceptualize mechanisms covering the dissolution of ASDs, formation of supersaturated ASD solutions, factors responsible for solution stabilization, drug uptake from ASD solutions, and drug distribution within these complex systems as well as effects of excipients. Furthermore, we discuss the importance of these findings on the development of ASDs. This improved overall understanding of these mechanisms will facilitate a rational ASD formulation development and will serve as a basis for further mechanistic research on drug delivery by ASDs.

show abstract

“…The formation of a drug-rich phase and a polymer-rich phase has been shown to negatively influence the dissolution behavior as upon AAPS, a congruent release of drug and polymer could turn into an undesirable incongruent release of drug and polymer (50,51). An incongruent release could lead to the fact that the dissolution is drugcontrolled which was shown to profoundly decrease the dissolution rate of an ASD (48,52). These findings are in line with the observations within our study and explain the decreased dissolution rate after exposure to acidic medium.…”

Section: Phase Separation Upon Immersion In Hydrochloric Acidmentioning

confidence: 99%

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

2021

View full text Add to dashboard Cite

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%.

show abstract

Congruent release of drug and polymer: A “sweet spot” in the dissolution of amorphous solid dispersions

Cited by 120 publications

References 40 publications

Impact of HPMCAS on the Dissolution Performance of Polyvinyl Alcohol Celecoxib Amorphous Solid Dispersions

Impact of HPMCAS on the Dissolution Performance of Polyvinyl Alcohol Celecoxib Amorphous Solid Dispersions

Mechanisms of increased bioavailability through amorphous solid dispersions: a review

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

Contact Info

Product

Resources

About