Influence of polymer molecular weight on in vitro dissolution behavior and in vivo performance of celecoxib:PVP amorphous solid dispersions

Knopp, Matthias Manne; Nguyen, Julia Hoang; Becker, Christian F. W.; Francke, Nadine Monika; Jørgensen, Erling B.; Holm, Per; Holm, René; Mu, Huiling; Rades, Thomas; Langguth, Peter

doi:10.1016/j.ejpb.2016.02.007

Cited by 66 publications

(39 citation statements)

References 49 publications

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“…Furthermore, the M w of the polymer has also been shown to affect the dissolution rate and performance of the drug from an ASD. Here, increasing the M w of PVP decreased the dissolution rate of celecoxib compared to PVP with lower M w [9]. Nevertheless, the ASDs with the lower M w PVP did not display the best overall dissolution performance (area under the dissolution-time curve) due to an inferior precipitation-inhibiting effect compared to the ASDs containing higher M w PVP.…”

Section: Introductionmentioning

confidence: 85%

Influence of the Polymer Glass Transition Temperature and Molecular Weight on Drug Amorphization Kinetics Using Ball Milling

et al. 2020

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In this study, the putative correlation between the molecular mobility of a polymer and the ball milling drug amorphization kinetics (i.e., time to reach full drug amorphization, ta) was studied using different grades of dextran (Dex) and polyvinylpyrrolidone (PVP) and the two model drugs indomethacin (IND) and chloramphenicol (CAP). In general, IND had lower ta values than CAP, indicating that IND amorphized faster than CAP in the presence of the polymers. In addition, an increase in polymer molecular weight (Mw) also led to an increase in ta for all systems investigated up to a critical Mw for each polymer, which was in line with an increase of the glass transition temperature (Tg) up to the critical Mw of each polymer. Hence, the increase in ta seemed to correlate well with the Tg/Mw of the polymers, which indicates that the polymers’ molecular mobility had an influence on the drug amorphization kinetics during ball milling.

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Section: Introductionmentioning

confidence: 85%

Influence of the Polymer Glass Transition Temperature and Molecular Weight on Drug Amorphization Kinetics Using Ball Milling

et al. 2020

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“…However, there is no report about a binary ASD consisting of CXB and HPMCAS, which reached as high a concentration as theoretically expectable based on the precipitation inhibitory potential. On the contrary, it was shown that ASDs consisting of CXB combined with a rather hydrophilic polymer like povidone or copovidone exhibited a fast dissolution rate but limited potential to maintain the generated supersaturation without addition of further precipitation inhibitors [26,27]. This proves the fact that the choice of suitable combinations of drug and polymer is complex and has to be carried out with care.…”

Section: Introductionmentioning

confidence: 99%

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

Monschke

Wagner

2020

Pharmaceutics

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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.

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“…In addition, insoluble carriers have also been exploited in many formulations of SDs. By taking advantage of hydrophobic interactions between polymers and poorly water-soluble drugs, the polymer may easily change the drug crystallinity into an amorphous state via molecular interactions, enhancing dissolution [42][43][44][45][46][47][48]. Moreover, the insoluble property of carriers in various dissolution media might be applied to overcome the low bioavailability of drugs with pH-independent solubility.…”

Section: Introductionmentioning

confidence: 99%

Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs

Tran

2020

Polymers

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In recent decades, solid dispersions have been demonstrated as an effective approach for improving the bioavailability of poorly water-soluble drugs, as have solid dispersion techniques that include the application of nanotechnology. Many studies have reported on the ability to change drug crystallinity and molecular interactions to enhance the dissolution rate of solid dispersions using hydrophilic carriers. However, numerous studies have indicated that insoluble carriers are also promising excipients in solid dispersions. In this report, an overview of solid dispersion strategies involving insoluble carriers has been provided. In addition to the role of solubility and dissolution enhancement, the perspectives of the use of these polymers in controlled release solid dispersions have been classified and discussed. Moreover, the compatibility between methods and carriers and between drug and carrier is mentioned. In general, this report on solid dispersions using insoluble carriers could provide a specific approach and/or a selection of these polymers for further formulation development and clinical applications.

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Influence of polymer molecular weight on in vitro dissolution behavior and in vivo performance of celecoxib:PVP amorphous solid dispersions

Cited by 66 publications

References 49 publications

Influence of the Polymer Glass Transition Temperature and Molecular Weight on Drug Amorphization Kinetics Using Ball Milling

Influence of the Polymer Glass Transition Temperature and Molecular Weight on Drug Amorphization Kinetics Using Ball Milling

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

Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs

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