Phase transition studies of dutasteride crystalline forms

Dutasteride (DU) (5α-reductase inhibitor) that is used for the treatment of benign prostate hyperplasia (BPH), DU has low water solubility and poor oral absorption that classified as Biopharmaceutics Classification System (BCS) class II. This study aims to improve the physical properties of Dutasteride (DU) like solubility by the preparation of microsponge (MS). Microsponges are spherical in shape, sponge-like structure, polymeric delivery systems composed of porous microspheres with a large internal surface area. Nine formulations of DU MS had been prepared by the technique of quasi-emulsion solvent diffusion (QESD) and utilizing Eudragit S100 as major polymer and glycerol as a plasticizer that dissolved in dichloromethane where polyvinyl alcohol PVA serves as a stabilizer in the external phase. The formulas were employed to optimize preparation variable factors include; different drug to polymer ratio, the addition of different concentrations of PVA, and stirring rate. Optimization was done using the response of production yield (PY), entrapment efficiency EE), particle size, and in vitro drug release; The results display that the best ratio of (drug: polymer) was 5:1, and the best rate of stirring was 1,000 rpm respecting the optimum characteristics of microsponge. The best-selected formula prepared (F2) was underwent to evaluation regarding saturated solubility, FTIR, DSC, and SEM and showed 1.28 folds enhancement in saturated solubility compared to plain DU, and was well fabricated with high entrapment efficiency (83.7% ± 1.37), production yield (85.61% ± 0.6), and particle size of 77μm. Moreover, the percent release of DU was 75.74 ± 1.5 after 4 hours, with good compatibility as confirmed by XRD, SEM, DSC, and fourier-transform infrared spectroscopy (FTIR) analysis. It can be concluded that the selected formula prepared (F2) of DU microsponge is reassuring and promising drug delivery with improved pharmaceutical physical properties.

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“…The study was confirmed by powder X-ray diffraction (XRD-6000, Shimadzu, Japan 220V/50Hz) at a continuous scan range of 2θ = 5 -80º. 26…”

Section: Powder X-ray Diffraction (Xrd) Studiesmentioning

confidence: 95%

Enhancement Solubilization of Dutasteride using Microsponge Formulation

Taghi¹,

Abdulbaqi²,

Ghazy³

2020

ijddt

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“…Other methods, including e.g. differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) as well as Raman (RS) and infrared spectroscopes (IR), help to further characterize the crystalline and amorphous forms.In this presentation, a few examples of phase transition studies in the active substances and solid dosage forms will be discussed: structural and physicochemical studies of olopatadine hydrochloride conformational polymorphs, phase transitions of dutasteride performed by the VT-XRPD method [2], erlotynib polymorphism studies performed by means of RS and the evaluation of analytical methods for the detection of phase transitions in tablets containing aripiprazole [3] and imatinib [4]. …”

mentioning

confidence: 99%

Detection of phase transitions in the studies of active substances and solid dosage forms

Łaszcz

Trzcińska

Witkowska

2016

Preprint

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Polymorphism is the ability of a compound in the solid state to exist in different crystalline forms. Molecules, having the same chemical composition, exhibit different spatial arrangements and/or exist in different configurations and conformations [1]. In pseudopolymorphs (solvates) molecules of solvents are incorporated into the crystal lattice. Contrary to the crystalline forms of polymorphs, amorphous forms are characterized by the lack of long-range molecule arrangements. The spatial arrangement of molecules in an active substance determines its physical properties and influences the bioavailability and stability of a drug product. The most frequent phase transitions that can be present in an active substance include: polymorphic transition, hydration, dehydration, amorphisation and crystallization. The knowledge about the phase transitions which can arise during the active substance manufacturing, formulation process and stability studies is very important. Phase transitions may lead to the formation of an undesirable phase of the active substance with different properties than its desirable form. Studies of phase transitions in an active substance contained in a solid dosage form are very complicated, because there are many additional factors to consider, including a small concentration of the active substance, the presence of crystalline and amorphous placebo constituents, as well as the interactions between the active substance and the excipients.There are a number of methods used to characterize crystalline and amorphous forms of the active substance. A definitive evidence of polymorphism or pseudopolymorphism is the demonstration of a nonequivalent structure by single crystal X-ray diffraction. X-ray powder diffraction (XRPD) and variable temperature X-ray powder diffraction (VT-XRPD) can also be used to provide an unequivocal proof of polymorphism and pseudopolymorphism. Other methods, including e.g. differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) as well as Raman (RS) and infrared spectroscopes (IR), help to further characterize the crystalline and amorphous forms.In this presentation, a few examples of phase transition studies in the active substances and solid dosage forms will be discussed: structural and physicochemical studies of olopatadine hydrochloride conformational polymorphs, phase transitions of dutasteride performed by the VT-XRPD method [2], erlotynib polymorphism studies performed by means of RS and the evaluation of analytical methods for the detection of phase transitions in tablets containing aripiprazole [3] and imatinib [4]. AcknowledgementsOlopatadine studies were supported by the European and Regional Funds under the project

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DSC of Low Molecular Mass Organic Materials and Pharmaceuticals

Wesołowski

2023

The Handbook of Differential Scanning Calorimetry

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Phase transition studies of dutasteride crystalline forms

Cited by 6 publications

References 20 publications

Enhancement Solubilization of Dutasteride using Microsponge Formulation

Enhancement Solubilization of Dutasteride using Microsponge Formulation

Detection of phase transitions in the studies of active substances and solid dosage forms

DSC of Low Molecular Mass Organic Materials and Pharmaceuticals

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