The objectives of this study were to prepare and characterize a novel piperine–succinic acid multicomponent crystal phase and to evaluate the improvement in the solubility and dissolution rate of piperine when prepared in the multicomponent crystal formation. The solid-state characterization of the novel multicomponent crystal was performed by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform-infrared (FT-IR) spectroscopy. Solubility and dissolution rate profiles were evaluated in distilled water. The physical stability was evaluated under high relative humidity (75% and 100% RH). The determination of the single crystal X-ray diffraction structure revealed that this novel multicomponent crystal was a cocrystalline phase of piperine–succinic acid (2:1 molar ratio). The differential scanning calorimetry thermogram of the cocrystal showed a single and sharp endothermic peak at 110.49 °C. The cocrystal resulted in greater solubility and a faster dissolution rate of piperine than intact piperine. This improvement was a result of the formation of a channel structure in the cocrystal. In addition, the cocrystal was stable under a humid condition.

No abstract

SUsnic acid is the secondary metabolite found in lichens, particularly Usnea sp which has considerable pharmacological activities. However, the used of usnic acid is still limited due to poorly soluble in water. The aim of this study was to investigate the impact of milling process to physicochemical properties of usnic acid. Usnic acid was isolated from Usnea sp by soxhlet extraction method. The crystal of usnic acid was then milled in three different times: 30, 60 and 90 minutes. The characterization of intact and milled usnic acid were conducted using powder X-ray diffraction (PXRD), infra-red spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Solubility test was conducted in water for 24 h and the amount of usnic acid was determined by UV spectrophotometry. The X-ray diffractogram showed a decline in peak intensity of usnic acid after milling process. The infra-red spectrum showed no shift of wavenumber of usnic acid after milling process. Thermal analysis showed a decline in melting point and heat energy of usnic acid after milling process. The photomicrograph of SEM depicted the changes in habit crystal of milled usnic acid. The solubility of intact usnic acid was 51 µg/ml, while the milled usnic acid increased fourfold compared to intact usnic acid. There was no significant difference of milling time on solubility (p>0.05). In conclusion, the milling process influence the physicochemical properties of usnic acid which indicated by crystallinity, melting point, crystal habit and solubility.

Piperine, a secondary metabolite of Piper nigrum L., has been known for its pharmacological activities. However, the use of piperine is still limited due to the low solubility in water. The aim of this study was to improve the physicochemical properties of piperine by preparing into multicomponent crystal (MC) using saccharin by solvent evaporation method, and ethanol was used as the solvent. The intact materials and MC were characterized by several solid-state instruments. The amount of dissolved piperine was determined by High Performance of Liquid Chromatography (HPLC) using acetonitrile: water (90:10) as the mobile phase. Both morphology of intact piperine and MC showed irregular crystals. The diffractogram showed that MC had new and specific peaks at 2Ɵ: 12.91, 15.04, 19.54 and 22.40. The thermogram presented melting point for intact piperine, saccharin and MC which were 132.81°C, 230.02°C, 197.09°C, respectively. The infra-red spectrum showed no significant shift of MC which indicated no chemical interaction between piperine and saccharin. The dissolution study pointed higher amount of piperine dissolved in 0.1 N HCl with addition of 0.5% sodium lauryl sulphate. The dissolution piperine in MC after 60 minutes was 81.29±5.91%, while intact piperine was 44.78±1.89%. In conclusion, the formation of multicomponent crystal of piperine-saccharin was able to increase the dissolution of piperine.

Amorphous solid dispersions of a poorly water-soluble drug genistein in PVP K-30 were prepared by solvent co-evaporation technique using organic solvent methanol. Solid dispersions system was prepared with several variations of the drug to polymer 2:1, 1:1 dan 1:2 w/w. Solid state properties of solid dispersion system were evaluated by powder X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry, and microscopic SEM. Dissolution rate profile was conducted in distilled water medium by using dissolution tester apparatus type II USP. Base on X-ray diffractometry analysis, differential scanning calorimetry and microscopic SEM, crystalline phase of genistein decreased in crystallinity index and formation of the amorphous state. Dissolution rate profile showed that genistein in amorphous solid dispersion had a faster dissolution rate in comparison to intact genistein. This study suggests that preparation of the solid dispersion of genistein in PVP K-30 is an effective approach to improve the dissolution rate of genistein. ABSTRAK:Sistem dispersi padat amorf senyawa obat yang sukar larut air genistein dalam PVP K-30 dibuat dengan metode penguapan pelarut menggunakan pelarut metanol. Sistem dispersi padat dibuat dengan variasi perbandingan obat : polimer 2:1, 1:1 dan 1:2 b/b. Sifat padatan serbuk sistem dispersi padat dievaluasi dengan metode analisa difraksi sinar-X, termal DSC, spektrokopik FT-IR dan mikroskopik SEM. Profil disolusi dilakukan dalam medium air suling dengan alat uji disolusi tipe II USP. Hasil analisa difraksi sinar-X, termal DSC dan mikroskopik SEM, fase kristalin genistein mengalami penurunan derajat kristalinitas dan pembentukan fase amorf. Profil laju disolusi menunjukkan bahwa sistem dispersi padat genistein memiliki laju disolusi yang lebih tinggi dibandingkan genistein murni. Studi ini membuktikan bahwa pembentukan sistem dispersi padat genistein dengan polimer PVP K-30 efektif memperbaiki laju disolusi genistein. Keywords 67 PENDAHULUANKelarutan dan laju disolusi senyawa obat yang rendah dalam air merupakan salah satu permasalahan besar dalam pengembangan dan manufaktur sediaan padat (tablet, kapsul) di industri farmasi. Lebih dari 80 % sediaan obat dipasaran adalah dalam bentuk tablet, dan 40 % dari senyawa obat tersebut memiliki kelarutan yang rendah dalam air, serta hampir 80 -90 % senyawa kandidat obat yang dalam tahap penelitian juga memiliki permasalahan kelarutan dan laju disolusi [1,2].Berdasarkan Biopharmaceutical classification system (BCS) senyawa obat diklasifikasi kedalam empat kategori, kelas I (kelarutan tinggi, permeabilitas tinggi), II (kelarutan rendah, permeabilitas tinggi), III (kelarutan tinggi, permeabilitas rendah dan kelas IV (kelarutan rendah, permeabilitas rendah) Senyawa obat yang masuk dalam kategori kelas II dan IV seringkali mengalami absorpsi yang rendah dalam cairan saluran pencernaan [3]. Berbagai strategi telah dilaporkan untuk memperbaiki laju disolusi senyawa obat kelas II dan IV ini, antara lain pembuata...

Tujuan penelitian ini adalah untuk meningkatkan laju disolusi piperin dengan pembentukan multikomponen kristal piperin dan asam nikotinat (1:1) dengan metode pelarutan menggunakan pelarut etanol. Multikomponen kristal dikarakterisasi sifat padatannya dengan Difraksi sinar-X, analisa termal Differential Scaning Calorimetry (DSC), spektroskopi FT-IR, analisa mikroskopik Scanning Electron Microscopy (SEM), uji kelarutan dan  profil laju disolusi menggunakan  Aparatus USP 2. Dari penelitian serbuk multikomponen kristal piperin-asam nikotinat diperoleh hasil  pola difraksi sinar-X menunjukkan puncak difraksi yang baru, analisa termal termogram DSC menunjukkan puncak endotermik pada 126,117 ºC, spektrum FTIR terdapat bilangan gelombang 3349,94 cm-1, analisa mikroskopik SEM menunjukkan sudah terbentuk agregat, uji kelarutan menunjukkan peningkatan 1,5 kali lipat dibandingkan piperin murni, profil laju disolusi piperin menunjukkan peningkatan secara signifikan dibandingkan piperin murni yaitu sekitar 2,5 kali lipat. Secara umum preparasi multikomponen kristal piperin-asam nikotinat dapat meningkatkan laju disolusi piperin

Usnic acid is a dibenzofuran derivate produced by some lichens species primarily Usnea sp., that has several pharmacological activities. Based on Biopharmaceutical Classification System (BCS), usnic acid belongs to class II that has high permeability but low solubility. Therefore, the purpose of this research was to increase the solubility of usnic acid by preparing solid dispersions (SD) using hydrophilic polymer HPMC 2910. Usnic acid and HPMC at ratio 1:1 (w/w) were prepared for solid dispersion using spray drying and freeze drying techniques. Physical mixture at the same ratio was prepared as comparison. Characterization for intact materials, physical mixture and solid dispersions were done using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), fourier transform infra-red (FT IR) spectroscopy, and solubility test. The result of PXRD showed a decrease of peak intensity for solid dispersions. Thermal properties of solid dispersions showed lower melting point compared to usnic acid and physical mixture. The morphology of solid dispersion depicted different shape compared to intact materials and physical mixture. The infra-red spectrum showed the slightly shift at wave numbers of functional groups but there was no new functional groups formed. The solubility of solid dispersions significantly increased, which the solubility test result were 55±0.023, 227±0.034, 567± 0.020, and 932±0.053 (μg/ml) for intact usnic acid, physical mixture, SD by spray drying and SD by freeze drying, respectively. In conclusion, solid dispersions of usnic acid – HPMC 2910 were able to modify physicochemical properties and increased the solubility.

The packing in olivetolic acid is similar to that in resorcinolic acid.