Gelucire can stabilize AET and improve its biopharmaceutical performance at a low excipient/drug ratio and may provide a better alternative to conventional stabilizers such as PVP.

One of the major challenges in pharmaceutical development is the poor dissolution performance of drugs. Celecoxib (CLX) is a poorly water soluble drug with its bioavailability being limited by its poor dissolution. In this study spray drying method was employed to prepare CLX: PVP K30:HPB (hydroxypropyl β-cyclodextrin) amorphous ternary system (ATS). Statistical experimental design was employed to investigate the combined effect of two experimental factors, i.e., % of polyvinayl pyrrolidone (PVP) K30 and % of HPB on saturation solubility (SS), dissolution efficiency (DE) and mean dissolution time (MDT), considered as the responses to be optimized. Design of experiment was used in the context of quality by design, which requires a multivariate approach for understanding the multifactorial relationships among experimental factors. Central composite design allowed for defining a design space. Desirability function was used to attain simultaneous optimization of all responses. The desired goals were achieved for SS, DE and MDT. Experimental values obtained from the optimized formulations were very close to the predicted values, thus confirming the validity of the generated mathematical model. These results demonstrated the effectiveness of the proposed jointed use of PVP K30 and HPB, as well as the usefulness of the multivariate approach for the preparation of ATS. Validated optimum ATS were characterized by DSC, XRD, SEM and particle size analysis. Characterization results confirmed the formation of amorphous ternary system with average particle size 727.9±260.6nm.

Methods of preparation and application of amorphous form are well established but it is equally important to note that devitrification of amorphous drugs has limited their applications. Present study was performed to investigate mechanism for amorphous drug stabilization using Gelucire in comparison with polyvinylpyrrolidone (PVP). Etoricoxib and celecoxib were taken as model drugs for this study, as etoricoxib has only proton accepting site for hydrogen bonding in comparison with celecoxib, which has both proton accepting and donating site. Solid dispersion of celecoxib with polyvinylpyrrolidone and Gelucire was prepared by spray drying and meltgranulation technique respectively. X-ray powder diffractometry and differential scanning calorimetry were used to study the physical state of the drug. Dissolution studies were performed to differentiate dissolution performance. Stability study samples were evaluated for physical state of the drug and dissolution performance. An IR study in correlation with molecular modeling was carried out to study the mechanism for stabilization. Dissolution of melt-granulation of amorphous celecoxib was improved significantly as compared to amorphous celecoxib and Celecoxib-PVP solid dispersion. Melt-granulation with lipid seemed to be more dominant than amorphization of drug for improving dissolution. Stability data revealed that PVP was significantly advantageous for amorphous form stabilization whereas Gelucire failed in case of Celecoxib. In contrast to this, our previous study revealed the stabilization ability of Gelucire for amorphous etoricoxib. Molecular modeling and IR studies revealed that H-bonding was predominant mechanism for stabilization. Out of two proposed mechanism for amorphous drug stabilization by lipids, H-bonding ability is more dominant than immobilization of molecule in lipid matrix.

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 ...

The aim of this study was to improve the mucoadhesive potential of xyloglucan polymer by the covalent attachment of cysteine as thiol moiety. The parent polymer xyloglucan was chemically modified by introducing sulphydryl bearing compound L-cysteine HCl. Different batches of xyloglucan-cysteine conjugates were prepared at varying reaction pH (2-6) and evaluated for optimum thiol incorporation, disulphide group content, swelling behavior, rheological properties and mucoadhesive properties. The obtained conjugates characterized in vitro by quantification of immobilized thiol groups; showed maximum thiol incorporation on xyloglucan (7.67 ± 0.14 %) at pH 5. The disulphide group content was found maximum (2.83 ± 0.12) at pH 6. The water uptake at end of 4 h was 5.0 for xyloglucan and was found to decrease in thiolated derivatives with increase in thiolation. Mucoadhesion studies revealed that mucoadhesion of xyloglucan-cysteine conjugate increased more than twice compared to the unmodified polymer. The viscosity of thiomer was more than that of xyloglucan because of formation of disulphide bonds.Uniterms: Mucoadhesion. Thiomer. Xyloglucan. L-cysteine HCl.O objetivo deste estudo foi melhorar o potencial mucoadesivo do polímero xiloglicano pela ligação covalente de cisteína como unidade de tiol. O polímero xiloglicano foi quimicamente modificado pela introdução de cloridrato de cisteína como grupo contendo sulfidrila. Prepararam-se diferentes lotes de conjugados cisteína-xiloglicano em pH variando de 2 a 6, avaliando-se a incorporação ótima de tiol, o conteúdo de dissulfeto, o comportamento de inchamento, as propriedades reológicas e mucoadesivas. Os conjugados obtidos foram caracterizados in vitro pela quantificação de grupos tiol, mostrando máxima incorporação na xiloglicana (7.67 ± 0.14 %) em pH 5. O conteúdo de grupos dissulfeto foi máximo (2.83 ± 0.12) em pH 6. O índice de inchamento em % no fim de 4 h foi 83.87 para o xiloglicano e diminuiu para os derivados tiolados. O conteúdo foi mínimo para TH2 (78.26), aumentou pouco até TH5 (83.33) e diminuiu, posteriormente, para TH6 (80.13). Os estudos de mucoadesão revelaram que o conjugado xiloglicano-cisteína aumentou mais que duas vezes comparativamente ao polímero não modificado. A viscosidade do tiômero foi maior do que a do xiloglicano devido à formação das ligações dissulfeto.