Study of Polymorphs of Progesterone by Novel Melt Sonocrystallization Technique: A Technical Note

Abstract

Abstract. A large number of pharmaceuticals exhibit polymorphism; 23% steroids, 60% sulfonamides, and 70% of barbiturates have shown this property. In this study, we have investigated and compared a new technique termed as melt sonocrystallization (MSC) with melt and sonocrystallization (SC) for induction of polymorphism in progesterone (PRG). Polymorphs were characterized by DSC, XRD, FT-IR, and FT Raman spectroscopy. Melt sonocrystallized progesterone (MSC-PRG) contained both the polymorphs, more soluble form II along with less soluble form I, whereas melt progesterone (M-PRG) and sonocrystallized progesterone (SC-PRG) contained only form I. Improvement in dissolution characteristics of both the polymorphs were compared and form II was found to be more readily soluble than form I in deionized water. Reduction in mean particle size of PRG during SC was also determined using laser diffractometer. During stability testing (40°C/75% RH) for 1 month, metastable form II of MSC-PRG was found to be transformed into its more stable state. MSC technique was thus found as a useful tool for induction of polymorphism.

Effect of ultrasound on the physico-chemical properties of poorly soluble drugs: Antisolvent sonocrystallization of ketoprofen

“…Moreover, particle agglomeration is significantly prevented [5]. US can be used as an alternative to the addition of a seed crystal and thus improving the crystal purity [20], and for the isolation of the most thermodynamically favored polymorph when applied to a polymorphic system [7,21,22]. ASC is reported to decrease the oiling out phenomenon and to facilitate the crystallization of materials difficult to nucleate [18,23].…”

The role of ultrasound in pharmaceutical production: sonocrystallization

“…The comparative study of melt sonocrystallization (MSC) with melt, and sonocrystallization (SC) for induction of polymorphism in progesterone was developed, and the polymorphs were characterized by DSC, XRD, FT‐IR and FT‐Raman spectroscopy, showing that melt sonocrystallized progesterone contained both polymorphs, more soluble form II along with less soluble form I, whereas melt progesterone and sonocrystallized progesterone contained only form I. Therefore, the last method was found to provide the best final product, as it also provided the less particle size and stability …”

“…Therefore, the last method was found to provide the best final product, as it also provided the less particle size and stability. [102] As the different polymorphs exhibit different solubilities, their prevalence in the solution can be controlled by the supersaturation level. This was the case of optimizing L-glutamic acid production, as this drug presents two polyphorms: the b-polymorph is stable (needle-shaped or flakeshaped crystals that difficult postprocessing), whereas the a-polymorph is metastable (prismatic or granular crystals that facilitated postprocessing).…”

Hydrophilic Matrix Based Oral Controlled Release Tablets of Melt Sonocrystallized Simvastatin

“…1 ml of the aqueous phase drug solution was taken separately from each funnel, diluted suitably and quantified spectrophotometrically. Partition coefficient was measured by using the formula (Tripathy andDas, 2013, Gupta et al, 2013); P = (C a -C b )/ C b Where, P= Partition coefficient, C a = Initial concentration of drug in aqueous phase (µg/ml) and C b = Final concentration of drug in aqueous phase after equilibrium (µg/ml) Flow property study SIM and MSCSIM forms were characterized for bulk density, tapped density, Carr's compressibility index, angle of repose and Hausner's ratio. Dynamic angle of repose of SIM and MSCSIM was determined by method reported by Gupta et al, where by placing 1 g of drug powder in a lab fabricated rotating cylinder apparatus and allowed to rotate at 25 rpm for 5 min.…”

“…. aspect to enhance its GI absorption and thereby, the bioavailability (Murtaza, 2012). Several techniques have been developed by researchers to increase the solubility profile of SIM, which includes Inclusion complex formation technique (Varshosaz et al, 2011, Shiralasetti et al, 2010, Solid dispersion technique (Zhang et al, 2011), Solubilisation by surfactant (Margulis-Goshen et al, 2009, Meng et al, 2007, Milling technique (Zimper et al, 2010), Nanoprecipitation (Patil et al, 2011) etc. Few of these techniques require an additional carrier or solvent which is undesirable.…”