Physicochemical Characterization of Hot Melt Extruded Bicalutamide–Polyvinylpyrrolidone Solid Dispersions

Andrews, Gavin; Abu-Diak, Osama A.; Jones, David S.

doi:10.1002/jps.21914

Cited by 113 publications

(90 citation statements)

References 29 publications

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“…The extrudates can be further processed into pellets as multi-particulate systems, films, or into tablets by milling and addition of tabletting excipients (16). Many polymers have been evaluated for use in HME including hydroxypropylcellulose (HPC) (17), polyvinyl pyrrolidone (18), polyethylene oxide (19), and sugars such as isomalt (20), erythritol (21), and mannitol (22). Being a process that is performed at high temperatures, the polymers and the drug have to meet the requirement of being thermoplastic, stable, and able to withstand the shear being exerted by the screws.…”

Section: Introductionmentioning

confidence: 99%

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology

Mohammed¹,

Majumdar

Singh

et al. 2012

AAPS PharmSciTech

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Abstract. The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

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Section: Introductionmentioning

confidence: 99%

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology

Mohammed¹,

Majumdar

Singh

et al. 2012

AAPS PharmSciTech

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“…The paddle speed was set at 50 rpm, while the temperature of the medium was maintained at 37±0.5°C. Samples of 5 mL were withdrawn at specific time points (0.5, 1, 2, 4,6,8,12,16,20, and 24 h without media replacement) and spectro-photometrically assessed by means of a double beam spectrophotometer (UV-1650PC, Shimadzu, Belgium; λ max MPT, MPS and MPF was 222, 222 and 220 nm respectively). The MPT, MPF or MPS content in the samples was determined by linear regression.…”

Section: In Vitro Drug Releasementioning

confidence: 99%

“…In addition, hot melt methods (i.e. hot melt extrusion and injection moulding) offer the possibility to disperse active pharmaceutical ingredients in a polymeric carrier in a highly controlled manner, yielding solid dispersions/solutions (8). These dosage forms aim at an improved dissolution rate and hence bioavailability of poorly soluble drugs; an area of increasing importance (9).…”

Section: Introductionmentioning

confidence: 99%

Preparation and Evaluation of Sustained-Release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding

et al. 2012

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Abstract. Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by injection moulding. The influence of process temperature; matrix composition; drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT), fumarate (MPF) and succinate (MPS) on ease of processing and drug release were evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest drug release, substituting part of Eudragit RL by RS resulted in slower drug release, all following first-order release kinetics. Drug load only affected drug release of matrices composed of Eudragit RS: a higher MPT concentration yielded faster release rates. Adding triethyl citrate enhanced the processability, but was detrimental to long-term stability. The process temperature and plasticizer level had no effect on drug release, whereas metoprolol salt form significantly influenced release properties. The moulded tablets had a low porosity and a smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment, thermal analysis and X-ray diffraction demonstrated the formation of a solid solution immediately after production, in which H-bonds were formed between metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high drug loadings of MPS and MPF showed a tendency to recrystallise during storage. The in vivo performance of injection-moulded tablets was strongly dependent upon drug loading.

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“…Therefore, albeit a daunting task, amorphous solid dispersions can be stabilized by rationally selecting the suitable polymeric carriers. The right polymer either by forming secondary interactions with the drug (18,19) or/and by their anti-plasticization effect, helps to stabilise the amorphous from by reducing their molecular mobility (20). Hence, the role of right polymers in developing acceptable solid dispersions is of extreme importance in stabilizing amorphous drugs.…”

Section: Introductionmentioning

confidence: 99%

Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

Verma

Rudraraju²

2015

AAPS PharmSciTech

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Abstract. Developing amorphous solid dispersions of water-insoluble molecules using polymeric materials is a well-defined approach to improve the dissolution rate and bioavailability. While the selected polymer plays a vital role in stabilizing the amorphous solid dispersion physically, it is equally important to improve the dissolution profile by inhibiting crystallization from the supersaturated solution generated by dissolution of the amorphous material. Furthermore, understanding the mechanism of dissolution rate enhancement is of vital importance. In this work, wetting kinetics was taken up as an alternative approach for understanding the enhanced dissolution rate for amorphous solid dispersion of a poorly soluble drug. While cilostazol (CIL) was selected as the model drug, povidone (PVP), copovidone, and hypromellose (HPMC) were the polymers of choice. The concentrations against time profiles were evaluated for the supersaturated solutions of CIL in the presence and absence of the selected polymers. The degree of supersaturation increased significantly with increase in polymer content within the solid dispersion. While povidone was found to maintain the highest level of supersaturation for the greatest length of time both in dissolution and solution crystallization experiments, copovidone and hypromellose were found to be the less effective as crystallization inhibitor. The ability of polymers to generate and maintain supersaturated drug solutions was assessed by dissolution studies. The wetting kinetics was compared against the solid dispersion composition to establish a correlation with enhanced dissolution rate.

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Physicochemical Characterization of Hot Melt Extruded Bicalutamide–Polyvinylpyrrolidone Solid Dispersions

Cited by 113 publications

References 29 publications

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology

Preparation and Evaluation of Sustained-Release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding

Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

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