Solid-State Stability and Characterization of Hot-Melt Extruded Poly(ethylene oxide) Films

Prodduturi, Suneela; Manek, Rahul V.; Kolling, William M.; Stodghill, Steven P.; Repka, Michael A.

doi:10.1002/jps.20437

Cited by 94 publications

(67 citation statements)

References 26 publications

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“…Hence, it would be very challenging to develop pure Soluplus® film formulations without adding a plasticizer. In addition, plasticizers are often added to a hot-melt extrusion formulation to improve the processing conditions during the manufacturing of the extruded dosage form, improve the physical and mechanical properties of the final product, and lower the glass transition temperature (Tg) of the polymer to avoid drug degradation that can occur at higher processing temperatures (5)(6)(7)(8). Thus, plasticizers will be needed to change thermal and mechanical properties in Soluplus® formulations to take full advantage of its potential as a solubilizer and solid dispersion carrier which has been demonstrated in other studies (1,2) Plasticizers are generally nonvolatile, high boiling, low molecular weight compounds added to a polymer to improve its processability, flexibility, and stretchability by modifying the mechanical properties making the films more ductile, lowering the melt viscosity and the Tg of the product without altering the fundamental chemical character of the plasticized material (9,10).…”

Section: Introductionmentioning

confidence: 99%

Plasticizer Effects on Physical–Mechanical Properties of Solvent Cast Soluplus® Films

2013

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Abstract. Soluplus® is a novel amphiphilic polymer that has been shown to enhance the solubility and drug dissolution rate of poorly soluble drugs. However, there still is a lack of information regarding the physical mechanical properties of Soluplus® with addition of the plasticizers. This study characterized the mechanical properties of Soluplus® with four different plasticizers. The plasticizers selected were polyethylene glycol 6, triethyl citrate, propylene glycol, and glycerin; they were studied at three different levels (15%, 20%, and 25% w/w). The effects of these plasticizers on the glass transition temperature, tensile strength, percent elongation, and Young's modulus of free films made from Soluplus® were measured and the toughness and ratio of tensile strength to Young's modulus were calculated. These results showed these four plasticizers are capable to plasticizing Soluplus® as indicated by the glass transition temperature lowering, tensile strength, and Young's modulus while increasing the percent elongation and film toughness. Among the plasticizers tested, polyethylene glycol 6 showed greatest changed in the mechanical properties studied.

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Section: Introductionmentioning

confidence: 99%

Plasticizer Effects on Physical–Mechanical Properties of Solvent Cast Soluplus® Films

2013

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“…Hence, while formulating poorly soluble drugs, lower molecular weight PEOs, which do not gel to a greater extent, may be advantageous due to lower diffusion path length for the drug. The bioadhesion and stability of the drugs incorporated in the polymer can also be influenced by the molecular weight (13).…”

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confidence: 99%

Preformulation Studies of a Prodrug of Δ9-Tetrahydrocannabinol

et al. 2008

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Abstract. Preformulation studies were performed on a hemiglutarate ester prodrug of Δ 9 -tetrahydrocannabinol (THC-HG), to facilitate the development of stable formulations by hot-melt methods. The various studies performed included solid-state thermal characterization, pKa, logP, aqueous and pH dependent solubility, pH stability and effect of moisture, temperature and oxygen on solid-state stability. A hot-melt method was utilized to fabricate THC-HG incorporated poly (ethylene oxide) (PEO) matrices and the bioadhesive properties, release profiles and post-processing stability of these matrices were assessed as a function of the polymer molecular weight. The prodrug exhibited a T g close to 0°C, indicating its amorphous nature. Thermogravimetric analysis revealed a rapid weight loss after 170°C. The prodrug exhibited a seven-fold higher aqueous solubility as compared to the parent drug (THC). Also, the solubility of the compound increased with increasing pH, being maximum at pH 8. The prodrug exhibited a v-shaped pH-rate profile, with the degradation rate minimum between pH 3 and 4. The moisture uptake and drug degradation increased with an increase in relative humidity. Solid-state stability indicated that the prodrug was stable at −18°C but demonstrated higher degradation at 4°C, 25°C and 40°C (51.6%, 74.5% and 90.1%, respectively) at the end of 3-months. THC-HG was found to be sensitive to the presence of oxygen. The release of the active from the polymeric matrices decreased, while bioadhesion increased, with an increase in molecular weight of PEO.

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“…Melting of semicrystalline polymers followed by solidification upon fast cooling may create larger amorphous region of the semicrystalline polymers (Prodduturi et al, 2005). To increase the amorphous content and ease the detection of glass transition of PEO, the unprocessed powder was heated above its melting point and then quench cooled in the DSC and DMTA instruments.…”

Section: Characterization Of Melt Extrudatesmentioning

confidence: 99%

“…Melting of PEO followed by solidification upon cooling may decrease PEO crystallinity, and hence increase the amorphous PEO fraction (Prodduturi et al, 2005). Molecular dispersions of drugs within semicrystalline polymers (solid solutions) can be formed by dissolution of drug molecules within the amorphous domain of these polymers rather than in the crystalline fraction (Janssens et al, 2008, Qing et al, 2010, Abu-Diak et al, 2012.…”

Section: Introductionmentioning

confidence: 99%

The Use of Binary Polymeric Networks in Stabilizing Polyethylene Oxide Solid Dispersions

Jones

Tian

Shu

et al. 2016

Journal of Pharmaceutical Sciences

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The objective of this study was to investigate the role of amorphous domain of polyethylene oxide (PEO), a semicrystalline polymer, on the stability of drug/PEO solid dispersion. Molecular dispersion of drugs within hydrophilic low molecular weights PEOs (solid solution) has been demonstrated as a viable approach to enhance the dissolution properties and hence the oral bioavailability of poorly soluble drugs. In this system, the drug molecules are dissolved within the amorphous domain of the polymer and a miscible amorphous drug/polymer combination can result in a decrease of the polymer crystallinity, and hence increasing its amorphous fraction. This may result in increasing the drug solubility in the polymer hence affecting the stability of drug/polymer solid dispersion system. PEO is a highly crystallisable semi-crystalline polymer in natural and a rapid decrease in the amorphous fraction of the polymer may occur immediately after hot-melt extrusion resulting a forced migration of amorphous drug into nearby amorphous region. Thus, the actual concentrations of the drug within PEO solid dispersion were much higher than the concentration that we intended. Therefore, we are proposing a novel method of stabilising the amorphous drug/PEO solid dispersion by stabilising the amorphous region of PEO using another amorphous polymer. Inclusion of a miscible polymer that can increase the glass transition (Tg) of PEO (antiplasticization) or/and form strong inter-polymer interactions was used to enhance the stability of the amorphous PEO. In this study, the effects of inter-polymer interactions and miscibility between PEO and an amorphous polymer of high Tg, Eudragit ® S100, on the stability of the amorphous PEO and consequently the PEO/drug celecoxib (CX) solid dispersion was studied. Hot-melt extrusion (HME) was used to prepare different ratios of binary polymer blends of PEO/S100 (70/30, 50/50 and 30/70 w/w) and ternary solid dispersion systems containing pre-defined drug loading within the PEO/S100 polymer blends. Results from differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis (DMTA) suggested a great miscibility between PEO and S100 polymer blends particularly in the 50/50 ratio. After immediately HME, single Tg was observed in all ternary systems that increase with increasing S100 amount (antiplasticization). The completely absence of PXRD crystalline Bragg's peaks also suggested the full amorphous CX/polymer solid dispersion has been produced. Upon storage, CX crystallized rapidly from the CX/PEO (30/70) system within 3 days at 40°C and 75% RH, whereas it remained stable without crystallization up to 4 weeks within CX/(PEO/S100) 30/(50/50) system. Interestingly, both the stability of the amorphous PEO and CX were greater in the ternary system containing the polymer blend at 50/50 ratio than other systems. Despite of the lower Tg of 30/(50/50) system than 30/(30/70) one, the former was more stable. This indicates that the antiplasticization effects by Eudragit ® S100 were not the ...

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Solid-State Stability and Characterization of Hot-Melt Extruded Poly(ethylene oxide) Films

Cited by 94 publications

References 26 publications

Plasticizer Effects on Physical–Mechanical Properties of Solvent Cast Soluplus® Films

Plasticizer Effects on Physical–Mechanical Properties of Solvent Cast Soluplus® Films

Preformulation Studies of a Prodrug of Δ9-Tetrahydrocannabinol

The Use of Binary Polymeric Networks in Stabilizing Polyethylene Oxide Solid Dispersions

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