Development of amorphous solid dispersion formulations of a poorly water-soluble drug, MK-0364

Sotthivirat, Sutthilug; McKelvey, Craig A.; Moser, Justin; Rege, Bhagwant D.; Xu, Wei; Zhang, D.

doi:10.1016/j.ijpharm.2013.04.037

Cited by 60 publications

(31 citation statements)

References 27 publications

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“…The temperatures ranged from 2°C to 60°C and the relative humidity varied between 0% and 100%. The duration also varied significantly, with stability studies lasting from 24 h to two years (73,74,81,82,84,86,88,92,93,104,105,109,110,113,115,116,118,120,123,124,126,127,129,130,132,134,135,139,143,146,149,153,158,166,169,172,175,176). While most of the studies did not mention the container used for the physical stability test, a few specified, for example, whether a closed or open container was used (88,92,113,123,132,146).…”

Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

“…In the reviewed articles, no specific method was used in the investigation of amorphous solubility and dissolution behavior, even though different pharmacopoeia methods provide general guidance on how they should be performed. Ninety-two of the 101 studies reported solubility and dissolution studies (71–74,77–79,81–92,95,97–107,109–111,113–119,121,123,124,126–133,135–139,141–154,156,157,160,161,166,168–176). The USP in vitro dissolution type II apparatus was the most commonly used instrument (67%), followed by the USP type I apparatus (6%), while the remaining 27% used various other apparatuses, including modified versions of the USP type I only (148) or paired with confocal Raman microscopy (98), USP types I and II apparatus (72), USP type IV (152), closed loop of USP types II and IV (152), a perspex flow cell (73,142), a rotary mixer (131), a Chinese pharmacopoeia type III apparatus (118), an in-house miniaturized USP type II apparatus (175), Sirius T3 apparatus (146), μFLUX dissolution-permeation apparatus (141), Raman UV-Vis flow cell system (99), a centrifuge (88), high throughput screening using a 96-well plate (82,115,157), Wood’s apparatus (99,137), an orbital shaking incubator (156), and another shake-flask method (171) (Fig.…”

Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

“…Likewise, the media reported were mainly different types of a simple buffers such as treated water (i.e. deionized, degassed, distilled, purified), HCl, and phosphate/acetate buffers at pHs ranging from 1.2 to 7.4 (71–74,77–79,81–88,90–92,95,100–107,109–111,113–119,121,126,127,129–133,135–139,149,150,153,154,156,160,161,166,168–177). Among the 88 studies that reported a dissolution assay, only sixteen (~18%) used a biorelevant dissolution medium (BDM) such as simulated gastrointestinal fluids and simulated saliva (77,79,82,97,121,123,130,135,136,145,152,154,160,169,170,176).…”

Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

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The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

2017

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The alarming numbers of poorly soluble discovery compounds have centered the efforts towards finding strategies to improve the solubility. One of the attractive approaches to enhance solubility is via amorphization despite the stability issue associated with it. Although the number of amorphous-based research reports has increased tremendously after year 2000, little is known on the current research practice in designing amorphous formulation and how it has changed after the concept of solid dispersion was first introduced decades ago. In this review we try to answer the following questions: What model compounds and excipients have been used in amorphous-based research? How were these two components selected and prepared? What methods have been used to assess the performance of amorphous formulation? What methodology have evolved and/or been standardized since amorphous-based formulation was first introduced and to what extent have we embraced on new methods? Is the extent of research mirrored in the number of marketed amorphous drug products? We have summarized the history and evolution of amorphous formulation and discuss the current status of amorphous formulation-related research practice. We also explore the potential uses of old experimental methods and how they can be used in tandem with computational tools in designing amorphous formulation more efficiently than the traditional trial-and-error approach.

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Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

See 1 more Smart Citation

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

2017

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“…The LLPS was also generated when danazol was added to aqueous media at concentrations above the amorphous solubility, and the addition of polymers greatly extended the lifetime of the supersaturated two-phase system (57). Additionally, the amorphous SD formulations of a poorly water-soluble drug, MK-0364, exhibit characteristics of a single-phase glass, including an amorphous halo (58). When the level of the precipitation inhibitor D-a-tocopheryl polyethylene glycol 1000 (TPGS 1000) is above 10%, the inclusion of TPGS 1000 in the PVPVA 64 carrier matrix will affect the dispersion of itraconazole at the molecular level, leading to the formation of drug clusters (59).…”

Section: Phase Transition or Separationmentioning

confidence: 99%

Bioavailability Improvement Strategies for Poorly Water-Soluble Drugs Based on the Supersaturation Mechanism: An Update

Yang¹,

Gong²,

Wang³

et al. 2016

J Pharm Pharm Sci

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-The formulation development for poorly soluble drugs still remains a challenge. Supersaturating drug delivery systems (SDDS) or drug delivery systems based on supersaturating provide a promising way to improve the oral bioavailability of poorly water-soluble drugs. In supersaturable formulations, drug concentration exceeds the equilibrium solubility when exposed to gastrointestinal fluids, and the supersaturation state is maintained long enough to be absorbed, resulting in compromised bioavailability. In this article, the mechanism of generating and maintaining supersaturation and the evaluation methods of supersaturation assays are discussed. Recent advances in different drug delivery systems based on supersaturating are the focus and are discussed in detail.

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“…Incomplete release of poorly water-soluble drugs from a formulation was another difficult issue hindering the development of SD (3). Numerous other reports have exhibited improvement in dissolution of SD by incorporating surfactants or the lack of complete dissolution due to absence of surfactants (17)(18)(19)(20). Serajuddin (3,16) showed that the incorporation of surfactant may be necessary in a SD formulation to ensure dispersion of such a liquid phase of drug in dissolution media as very fine globules so that the drug release may continue.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Polymer-Surfactant and Polymer-Drug-Surfactant Miscibility for Solid Dispersion

Gumaste

Gupta

Serajuddin

2016

AAPS J

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In a solid dispersion (SD), the drug is generally dispersed either molecularly or in the amorphous state in polymeric carriers, and the addition of a surfactant is often important to ensure drug release from such a system. The objective of this investigation was to screen systematically polymer-surfactant and polymer-drug-surfactant miscibility by using the film casting method. Miscibility of the crystalline solid surfactant, poloxamer 188, with two commonly used amorphous polymeric carriers, Soluplus® and HPMCAS, was first studied. Then, polymer-drug-surfactant miscibility was determined using itraconazole as the model drug, and ternary phase diagrams were constructed. The casted films were examined by DSC, PXRD and polarized light microscopy for any crystallization or phase separation of surfactant, drug or both in freshly prepared films and after exposure to 40°C/75% RH for 7, 14, and 30 days. The miscibility of poloxamer 188 with Soluplus® was <10% w/w, while its miscibility with HPMCAS was at least 30% w/w. Although itraconazole by itself was miscible with Soluplus® up to 40% w/w, the presence of poloxamer drastically reduced its miscibility to <10%. In contrast, poloxamer 188 had minimal impact on HPMCAS-itraconazole miscibility. For example, the phase diagram showed amorphous miscibility of HPMCAS, itraconazole, and poloxamer 188 at 54, 23, and 23% w/w, respectively, even after exposure to 40°C/75% RH for 1 month. Thus, a relatively simple and practical method of screening miscibility of different components and ultimately physical stability of SD is provided. The results also identify the HPMCAS-poloxamer 188 mixture as an optimal surface-active carrier system for SD.

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Development of amorphous solid dispersion formulations of a poorly water-soluble drug, MK-0364

Cited by 60 publications

References 27 publications

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

Bioavailability Improvement Strategies for Poorly Water-Soluble Drugs Based on the Supersaturation Mechanism: An Update

Investigation of Polymer-Surfactant and Polymer-Drug-Surfactant Miscibility for Solid Dispersion

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