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

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

Melt solidification technique: Incorporation of higher wax content in ibuprofen beads

The purpose of this study was to achieve incorporation of a higher amount of wax during the preparation of ibuprofen beads by a melt solidification technique for better integrity and prolonged drug release by using a combination of waxes. A mixture of cetyl alcohol (CA) and palmitic acid (PA) was used to improve the matrix integrity and drug release. The effect of variables such as CA, PA, and speed of agitation were studied using 33 factorial design. Yield, crushing strength, and drug release were analyzed using response surface methodology. The in vitro dissolution test did not show any significant improvement in the drug release. Scanning electron microscopy (SEM) showed that beads were spherical with a smooth surface, but after dissolution became rough and porous. Differential scanning calorimetry (DSC) studies showed that different solidification and erosion properties of waxes are responsible for the inability of waxes to retard drug release even at higher concentration

Agglomeration of ibuprofen with talc by novel crystallo-co-agglomeration technique

The purpose of this research work was to obtain directly compressible agglomerates of ibuprofen with talc by a novel crystallo-co-agglomeration (CCA) technique, which is an extension of spherical crystallization. Ibuprofen-talc agglomerates were prepared using dichloromethane (DCM)-water as the crystallization system. DCM acted as a good solvent for ibuprofen as well as a bridging liquid for agglomeration of crystallized drug with talc. The agglomerates were characterized by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy and were evaluated for tableting properties and for drug release. The process yielded spherical agglomerates containing ∼95% to 96% wt/wt of ibuprofen. Agglomerates containing talc showed uniform distribution of hydroxypropylmethylcellulose and decreased crystallinity, and deformed under pressure. The miniscular form of ibuprofen and the hydrophobicity of talc governed the drug release rate. The batch containing a higher proportion of talc showed zeroorder kinetics and drug release was extended up to 13 hours. The CCA technique developed in this study is suitable for obtaining agglomerates of drug with talc as an excipient

Crystallo-co-agglomeration: A novel technique to obtain ibuprofen-paracetamol agglomerates

The purpose of this research was to obtain directly compressible agglomerates of ibuprofen-paracetamol containing a desired ratio of drugs using a crystallo-co-agglomeration technique. Crystallo-co-agglomeration is an extension of the spherical crystallization technique, which enables simultaneous crystallization and agglomeration of 2 or more drugs or crystallization of a drug and its simultaneous agglomeration with another drug or excipient. Dichloromethane (DCM)-water system containing polyethylene glycol (PEG) 6000, polyvinyl pyrollidone, and ethylcellulose was used as the crystallization system. DCM acted as a good solvent for ibuprofen and bridging liquid for agglomeration. The process was performed at pH 5, considering the low solubility of ibuprofen and the stability of paracetamol. Loss of paracetamol was reduced by maintaining a low process temperature and by the addition of dextrose as a solubility suppressant. The agglomerates were characterized by differential scanning calorimetry, powder x-ray diffraction (PXRD), and scanning electron microscopy and were evaluated for tableting properties. The spherical agglomerates contained an ibuprofen-paracetamol ratio in the range of 1.23 to 1.36. Micromeritic, mechanical, and compressional properties of the agglomerates were affected by incorporated polymer. The PXRD data showed reduction in intensities owing to dilution and reduced crystallinity. Thermal data showed interaction between components at higher temperature. Ethylcellulose imparted mechanical strength to the agglomerates as well as compacts. The agglomerates containing PEG have better comparessibility but drug release in the initial stages was affected owing to asperity melting, yielding harder compacts. The agglomeration and properties of agglomerates were influenced by the nature of polymer

Preparation and characterization of etoricoxib solid dispersions using lipid carriers by spray drying technique

The basic objectives of this study were to prepare and characterize solid dispersions of poorly water-soluble drug etoricoxib using lipid carriers by spray drying technique. The properties of solid dispersions were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), differential scanning calorimetry (DSC), hotstage microscopy (HSM), radiograph powder diffraction (XRPD), and dissolution studies. The absence of etoricoxib peaks in XRPD profiles of solid dispersions suggests the transformation of crystalline etoricoxib into an amorphous form. In the HSM examination of solid dispersions, the dissolution of drug in the lipid carriers was observed, which was also confirmed by the absence of etoricoxib peak in DSC curves of solid dispersions. The DRIFTS spectra revealed the presence of hydrogen bonding in solid dispersions. The in vitro dissolution rate of solid dispersions as compared with pure etoricoxib, spray-dried etoricoxib, and physical mixtures of drug with lipid carriers. Therefore, the dissolution rate of poorly water-soluble drug etoricoxib can be significantly enhanced by the preparation of solid dispersions using lipid carriers by spray drying technique

Preparation and evaluation of diltiazem hydrochloride-gelucire 43/01 floating granules prepared by melt granulation

The basic objective of this study was to explore the application of Gelucire 43/01 for the design of multi-unit floating systems of a highly water-soluble drug diltiazem HCl. Diltiazem HCl-Gelucire 43/01 granules were prepared by melt granulation technique. The granules were evaluated for in vitro and in vivo floating ability, surface topography, and in vitro drug release. Aging effect on storage was vvaluated using scanning electron microscopy, hot stage polarizing microscopy (HSPM), differential scanning calorimetry (DSC), and in vitro drug release. Granules were retained in stomach at least for 6 hours. Approximately 65% to 80% drug was released over 6 hours with initial fast release from the surface. Surface topography, HSPM, DSC study of the aged samples showed phase transformation of Gelucire. The phase transformation also caused significant increase in drug release. In conclusion, hydrophobic lipid, Gelucire 43/01, can be considered as an effective carrier for design of a multi-unit floating drug delivery system of highly water-soluble drugs such as diltiazem HCl