Thermal investigation of crystallization of polyethylene glycols in solid dispersions containing oxazepam

Ginés, J. M.; Arias, María Trinidad García; Moyano, J. R.; Soto, Pedro J. Sánchez

doi:10.1016/s0378-5173(96)04702-3

Cited by 42 publications

(25 citation statements)

References 9 publications

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“…In another study, a metastable amorphous form of nifedipine was formed in its solid dispersions in PEG 4000 and PEG 6000 when the drug-carrier melts were cooled rapidly, whereas slow cooling of melts or powdering of solidified mass resulted in the crystallization of drug. 29 Ginés et al 30 studied the effect of fusion temperature on oxazepam-PEG 4000 solid dispersions. Microscopic examination revealed the presence of crystalline oxazepam and the spherulitic form of PEG 4000 in solid dispersions prepared by fusion at 100°C.…”

Section: Reproducibility Of Physicochemical Propertiessmentioning

confidence: 99%

“…Such changes in physical states of drugs in solid dispersions result into differences in drug dissolution rates in aqueous media. 30 Drug-to-carrier ratio and particle size of solid dispersions were also reported to influence the dissolution rate of drug. 32 The properties of solid dispersions prepared by the solvent method may also vary depending on manufacturing conditions.…”

Section: Reproducibility Of Physicochemical Propertiessmentioning

confidence: 99%

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Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs

Serajuddin

1999

Journal of Pharmaceutical Sciences

1,434

780

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Although there was a great interest in solid dispersion systems during the past four decades to increase dissolution rate and bioavailability of poorly water-soluble drugs, their commercial use has been very limited, primarily because of manufacturing difficulties and stability problems. Solid dispersions of drugs were generally produced by melt or solvent evaporation methods. The materials, which were usually semisolid and waxy in nature, were hardened by cooling to very low temperatures. They were then pulverized, sieved, mixed with relatively large amounts of excipients, and encapsulated into hard gelatin capsules or compressed into tablets. These operations were difficult to scale up for the manufacture of dosage forms. The situation has, however, been changing in recent years because of the availability of surface-active and self-emulsifying carriers and the development of technologies to encapsulate solid dispersions directly into hard gelatin capsules as melts. Solid plugs are formed inside the capsules when the melts are cooled to room temperature. Because of surface activity of carriers used, complete dissolution of drug from such solid dispersions can be obtained without the need for pulverization, sieving, mixing with excipients, etc. Equipment is available for large-scale manufacturing of such capsules. Some practical limitations of dosage form development might be the inadequate solubility of drugs in carriers and the instability of drugs and carriers at elevated temperatures necessary to manufacture capsules.

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Section: Reproducibility Of Physicochemical Propertiessmentioning

confidence: 99%

Section: Reproducibility Of Physicochemical Propertiessmentioning

confidence: 99%

Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs

Serajuddin

1999

Journal of Pharmaceutical Sciences

1,434

780

View full text Add to dashboard Cite

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“…Solid dispersions prepared at 150°C also exhibited faster dissolution rate compared to the systems prepared at 100°C. This was attributed to the dissimilarity in the physicochemical state of the drug and the discrepancy in the crystalline structure of the carrier [89].…”

Section: Combined Factorsmentioning

confidence: 99%

“…It has been found that the microstructure of solid dispersions made up of PEG and APIs is inherently complex and there is a huge variation in crystallization behavior, location, and domain size of dispersed APIs. Nifedipine [71] and haloperidol [93]were crystalline whereas oxazepam [89] and loratadine [93] were dissolved in the PEG matrix. Depending on the crystallization tendency of the API and the interaction between the API and PEG, the API can be located in interlamellar, interfibrillar, or interspherulitic regions or some combination of these regions in the PEG matrix, yielding different microstructures, which in turn gives rise to various material properties (Figure 4).…”

Section: Microstructure Of Semicrystalline Solid Dispersionsmentioning

confidence: 99%

The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers

Duong

Mooter

2016

Expert Opinion on Drug Delivery

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As a consequence of the target and drug candidate identification process, drugs with higher hydrophobicity and/or lipophilicity are being selected for further development, leading to solubility and dissolution rate limited oral bioavailability, and hence potential failure of the intended therapeutic goal. Solid dispersions were introduced as a formulation strategy in the early 1960s to tackle this issue and are still an area of intensive research activity. Areas covered: There has been a shift in the type of carriers that were used in the formulation of solid dispersions as nowadays, amorphous carriers are most often used, whereas in early stages of solid dispersions development, crystalline and semi-crystalline carriers were most commonly applied. In this review, we will discuss several aspects related to the use of crystalline and semi-crystalline carriers such as their molecular and related physical structure, and their physical chemical properties related to formulation of poorly soluble drugs. Expert opinion: The inherent crystallinity of this type of carrier hinders the formation of high-load solid solutions as mainly the amorphous domains of a carrier are able to accommodate drug molecules. Hence these carriers are not currently first choice excipients to formulate solid dispersions.

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“…The solvent method involves the solubilization of drug and carriers in a suitable solvent and forming coprecipitates after the evaporation of the solvent under a reduced pressure which is more acceptable for high-melting-point carriers like polyvinylpyrrolidones [3][4][5] . In solid dispersions, the drug can exist in microcrystalline state in eutectic mixtures 6,7 and amorphous or molecularly dispersed form in coprecipitates 8,9 . In both cases, improved drug dissolution rate by solid dispersion lies in the greatly enhanced surface area due to the changes in physical state of the incorporated drugs.…”

Section: Introductionmentioning

confidence: 99%

Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate

Kolašinac¹,

Kachrimanis²,

Djuriš³

et al. 2012

Drug Development and Industrial Pharmacy

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Solid dispersion systems have been widely used to enhance dissolution rate and oral bioavailability of poorly water-soluble drugs. However, the formulation process development and scale-up present a number of difficulties which has greatly limited their commercial applications. In this study, solid dispersions (SDs) of desloratadine (DSL) with povidone (PVP) and crospovidone (cPVP) were prepared by spray coating technique. The process involved the spray application of 96% ethanol solution of DSL and PVP/cPVP, and subsequent deposition of the coprecipitates onto microcrystalline cellulose pellets during drying by air flow in a mini spray coater. The results from the present study demonstrated that the spray coating process is efficient in preparing SDs with enhanced drug dissolution rate and it is highly efficient in organic solvent removal. Both PVP and cPVP greatly improved drug dissolution rate by SDs, with PVP showing better solubilization capability. Very fast drug dissolution rate is achieved from SDs containing PVP regardless of differences in K grade. SD with smaller particles of cPVP have higher drug dissolution rate in comparison to the cPVP with larger particles. Results from physical state characterization indicate that DSL in SDs exist in the amorphous (high free-energy) state which is probably stabilized by PVP/cPVP. After 6-month accelerated stability study, DSL remains amorphous, while PVP and cPVP act as anti-plasticizing agents, offering efficient steric hindrance for nucleation and crystal growth.

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Thermal investigation of crystallization of polyethylene glycols in solid dispersions containing oxazepam

Cited by 42 publications

References 9 publications

Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs

Solid dispersion of poorly water‐soluble drugs: Early promises, subsequent problems, and recent breakthroughs

The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers

Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate

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