Hydroxypropyl Methylcellulose Acetate Succinate: Potential Drug–Excipient Incompatibility

Dong, Zedong; Choi, Duk Soon

doi:10.1208/s12249-008-9138-5

Cited by 41 publications

(18 citation statements)

References 10 publications

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“…In this case, the concentration of VAL decreased and a new peak appeared in the chromatogram, which we attribute to a degradation product. Hydroxypropyl methycellulose, a coating agent and rate-controlling polymer for sustained release formulations, may react with the hydroxyl group of VAL (Dong et al, 2008).…”

Section: Stability and Compatibility Assaymentioning

confidence: 99%

Compatibility and stability of valsartan in a solid pharmaceutical formulation

Julio

Zâmara

Garcia

et al. 2013

Braz. J. Pharm. Sci.

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Valsartan (VAL) is a highly selective blocker of the angiotensin II receptor that has been widely used in the treatment of hypertension. Active pharmaceutical ingredient compatibility with excipients (crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose and titanium dioxide) is usually evaluated in solid pharmaceutical development. Compatibility and stability can be evaluated by liquid chromatography. Studies were performed using binary mixtures of 1:1 (w/w) VAL/excipient; samples were stored under accelerated stability test conditions (40 °C at 75% relative humidity). The results indicate that VAL is incompatible with crospovidone and hypromellose, which reduced the VAL content and gave rise to new peaks in the chromatogram due to degradation products. Valsartana (VAL) é um bloqueador altamente seletivo do receptor da angiotensina II, que tem sido amplamente utilizado para o tratamento da hipertensão. Testes de compatibilidade com excipientes usualmente empregados em formulações sólidas são utilizados no desenvolvimento de formulações sólidas. Neste trabalho, realizaram-se testes utilizando misturas binárias na proporção 1:1 (m/m) de VAL/excipiente e as amostras foram armazenadas em condições de estabilidade acelerada (40 °C em 75% de umidade relativa). Os resultados obtidos indicam a incompatibilidade de VAL com crospovidona e hipromelose, através da redução do teor de VAL e a presença de novos picos no cromatograma provenientes de produtos de degradação.Unitermos: Valsartana/compatibilidade. Valtasan/estabilidade. Hipertensão/tratamento. Calorimetria Exploratória Diferencial/análise de fármacos. Cromatografia líquida de alto desempenho/análise quantitativa.

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Section: Stability and Compatibility Assaymentioning

confidence: 99%

Compatibility and stability of valsartan in a solid pharmaceutical formulation

Julio

Zâmara

Garcia

et al. 2013

Braz. J. Pharm. Sci.

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“…However, optimizing processing conditions can only minimize degradation to a certain extent. This is because chemical degradation may occur from the incompatibilities of formulation excipients with API (i.e., polymeric acetate groups promoting ester hydrolysis of the API) (29)(30)(31). When minimizing thermal degradation, the optimization process can be achieved efficiently and effectively using in-line PAT, as discussed in the later section.…”

Section: Introductionmentioning

confidence: 99%

Innovations in Thermal Processing: Hot-Melt Extrusion and KinetiSol® Dispersing

Tan

Davis

Miller³

et al. 2020

AAPS PharmSciTech

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Thermal processing has gained much interest in the pharmaceutical industry, particularly for the enhancement of solubility, bioavailability, and dissolution of active pharmaceutical ingredients (APIs) with poor aqueous solubility. Formulation scientists have developed various techniques which may include physical and chemical modifications to achieve solubility enhancement. One of the most commonly used methods for solubility enhancement is through the use of amorphous solid dispersions (ASDs). Examples of commercialized ASDs include Kaletra®, Kalydeco®, and Onmel®. Various technologies produce ASDs; some of the approaches, such as spray-drying, solvent evaporation, and lyophilization, involve the use of solvents, whereas thermal approaches often do not require solvents. Processes that do not require solvents are usually preferred, as some solvents may induce toxicity due to residual solvents and are often considered to be damaging to the environment. The purpose of this review is to provide an update on recent innovations reported for using hot-melt extrusion and KinetiSol® Dispersing technologies to formulate poorly water-soluble APIs in amorphous solid dispersions. We will address development challenges for poorly water-soluble APIs and how these two processes meet these challenges.

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“…The selection of the model compounds was based on their expected reactivity with PVAP and their degradation products. Dipyridamole (DPD) contains alcoholic groups which are prone to undergo heat-induced esterification [39]. Indomethacin (IND) on the contrary has no reactive groups like alcohols or primary/secondary amines and is therefore expected to stay stable.…”

Section: Introductionmentioning

confidence: 99%

Processing of Polyvinyl Acetate Phthalate in Hot-Melt Extrusion—Preparation of Amorphous Solid Dispersions

2020

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The preparation of amorphous solid dispersions (ASDs) is a suitable approach to overcome solubility-limited absorption of poorly soluble drugs. In particular, pH-dependent soluble polymers have proven to be an excellently suitable carrier material for ASDs. Polyvinyl acetate phthalate (PVAP) is a polymer with a pH-dependent solubility, which is as yet not thoroughly characterized regarding its suitability for a hot-melt extrusion process. The objective of this study was to assess the processability of PVAP within a hot-melt extrusion process with the aim of preparing an ASD. Therefore, the influence of different process parameters (temperature, feed-rate) on the degree of degradation, solid-state and dissolution time of the neat polymer was studied. Subsequently, drug-containing ASDs with indomethacin (IND) and dipyridamole (DPD) were prepared, respectively, and analyzed regarding drug content, solid-state, non-sink dissolution performance and storage stability. PVAP was extrudable in combination with 10% (w/w) PEG 3000 as plasticizer. The dissolution time of PVAP was only slightly influenced by different process parameters. For IND no degradation occurred in combination with PVAP and single phased ASDs could be generated. The dissolution performance of the IND-PVAP ASD at pH 5.5 was superior and at pH 6.8 equivalent compared to commonly used polymers hydroxypropylmethylcellulose acetate succinate (HPMCAS) and Eudragit L100-55.

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Hydroxypropyl Methylcellulose Acetate Succinate: Potential Drug–Excipient Incompatibility

Cited by 41 publications

References 10 publications

Compatibility and stability of valsartan in a solid pharmaceutical formulation

Compatibility and stability of valsartan in a solid pharmaceutical formulation

Innovations in Thermal Processing: Hot-Melt Extrusion and KinetiSol® Dispersing

Processing of Polyvinyl Acetate Phthalate in Hot-Melt Extrusion—Preparation of Amorphous Solid Dispersions

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