Application of Polyglycolized Glycerides in Protection of Amorphous Form of Etoricoxib during Compression

Abstract

Amorphous form of poorly water-soluble drugs lead to marked improvement in their dissolution and thus their relative bioavailability. Many reports on preparation and stabilization of amorphous form have been documented in the literature. Solid dispersion of itraconazole, prepared by spraying the drug and hydroxypropyl methyl cellulose (HPMC) on neutral pellets using organic solvent, is marketed in the trade name of Sporanox ® . Similarly solid dispersion of griseofulvin in PEG (Gris-PEG, Novartis) and Nobilon in povidone (Cesamet, Lilly) was marketed.Despite of this its commercial potential has been limited because of problem in processing of solid dispersions in the suitable dosage form like tablet. Development of solid dispersion into convenient dosage form for their clinical use and successful commercialization is a major challenge for pharmaceutical scientists. Amorphous drug prepared by super critical fluid precipitation has been formulated in the inhalers/spray. Akbuga et al. reported tablets of furosemide-PVP solid dispersion but it has limitations like large amount of disintegrants were required for disintegration of tablet 2) compression difficulties were encountered due to sticking to punches and dies.3) Pirttimaki et al. reported the polymorphic transformation of caffeine in the tableting, 4) because during tableting material obtains energy from mechanical pharmaceutical operations like mixing, grinding, granulation, drying and tableting necessary for transformation.In an effort to prevent polymorphic transformation of amorphous indomethacin and stabilization of enzymes, Picker et al. has evaluated carrageenan, a polymer with high viscoelastic property. It was found to be superior to microcrystalline cellulose, the effect was attributed to the high elasticity of carrageenan during tableting.5-7) Schmidt et al. 8) have reported the potential of polyethylene oxides for protection of amorphous indomethacin due to tableting. Similarly, heterogeneous system containing lipids has been reported for enzyme stabilization in the tablet form. 9) Recently, Shimpi et al. 10) have reported stabilization of amorphous form of etoricoxib in the melt granules with low amount of polyglycolized glycerides (Gelucire) 50/13. The stabilization has been attributed to H-bonding between Gelucire and drug and immobilization of the molecule in the matrix.In the present study it is hypothesized that Gelucires can offer elasticity and protects amorphous form during compression and shelf life. Aim of the present study was to evaluate the effect of compression on the stability of amorphous etoricoxib. Our earlier study on the melt granules revealed that Gelucire 50/13 has the stabilizing ability for amorphous etoricoxib in the ratio of 1 : 0.5 w/w. ExperimentalMaterials Etoricoxib (ET) was obtained as a gift sample from Unichem Laboratories Ltd. (Mumbai, India). Gelucire ® 50/13 (Stearoyl Macrogoglycerides EP, Gattefosse, France) and Avicel PH 102 (microcrystalline cellulose) were supplied by Colorcon India (Mumbai, India) and ...

Formulation Development of Mouth Dissolving Film of Etoricoxib for Pain Management

“…Figure 3. Melting of etoricoxib in DSC starts at 137 ∘ C. DSC curve of etoricoxib exhibited a broad endothermic peak at 147.15 ∘ C, starting at which is ascribed to drug melting [27]. DSC curve of beta-cyclodextrin exhibited a broad endothermic peak at 160 ∘ C, which is due to its dehydration of bound water.…”

Physicochemical Investigations and Stability Studies of Amorphous Gliclazide

“…Drug amorphization is an interesting and frequently being exploited one of the approaches for enhancement of physicochemical and biopharmaceutical characteristics of poorly aqueous soluble crystalline active pharmaceutical ingredients (APIs) (1)(2)(3)(4). Due to inherent and thermodynamic stability of crystalline API, it is usually being preferred for the purpose of delivery by the formulation experts in a pharmaceutical industry (5-7).…”

Polymorphism and Solvatomorphism 2007

“…The amorphous state of indomethacin has been maintained in solid dispersions containing crospovidone, and evidence was presented that suggested the existence of an interaction between the functional groups of the drug substance and the amide carbonyl group of the excipient 219. In another study, the ability of polyglycolized glycerides to protect etoricoxib in its amorphous state was evaluated after production of melt granules and tablets 220. The ability of the excipient to be easily tabletted at low compaction pressures and its degree of elastic recovery provided the necessary stabilization, presumably by protecting the particles of amorphous drug substance from the compression forces.…”