Retno Sari

ÖZ Amaç: Kersetin, polihidroksiaromatik yapılı flavonoidlerden biridir. Kersetinin oksidatif strese karşı bir biyoaktivite sergilediği ileri sürülmüştür. Ancak, kersetin sulu ortamda zayıf çözünürlüğe sahiptir. Bu çalışmanın amacı kersetin-süksinik asit ko-kristalin fiziko-kimyasal özelliklerini ve çözünme oranlarını araştırmaktır. Gereç ve Yöntemler: Kersetin-süksinik asit ko-kristali 1:1 molar oranında çözücü buharlaştırma ile hazırlanmıştır. Kersetin-süksinik asit ko-kristalinin fiziko-kimyasal özelliklerini belirlemek için X-ışını kırınımı, diferansiyel termal analiz, kızıl ötesi spektroskopi ve taramalı elektron mikroskopu kullanılmıştır. Çözünme, %2 SLS içeren sitrat tamponu içinde 100 rpm ve 37°C'de USP II (palet) aparatında 60 dakika çalışılmıştır. Bulgular: Difraktogram, termogram, IR vemikroskobik tespite dayanarak, kersetin-süksinik asit ko-kristalin fiziko-kimyasal özelliklerinin kersetinden farklı olduğu görülmüştür. Ek olarak, in vitro çözünme testi, ko-kristalin çözünme profilinin saf kersetinden çok daha yüksek olduğunu göstermiştir. Sonuç: Bu nedenle bu çalışma, çözücü buharlaştırma kullanılarak kersetin-süksinik asit ko-kristalinin oluşumunun kersetinin fiziko-kimyasal özelliklerini ve çözünme oranını artırdığını düşündürmektedir. Anahtar kelimeler: Karakterizasyon, çözünme, ko-kristal, kersetin, süksinik asit, çözücü buharlaştırma Objectives: Quercetin is one of the flavonoids with a polyhydroxyaromatic structure. Quercetin has been proposed to exhibit a bioWactivity against oxidative stress. However, quercetin has poor solubility in aqueous media. The purpose of this study was to investigate the physicochemical properties and dissolution rates of quercetin-succinic acid co-crystals. Materials and Methods: The quercetin-succinic acid co-crystals were prepared in 1:1 molar ratio using solvent evaporation. X-ray diffraction, differential thermal analysis, infrared spectroscopy, and scanning electron microscopy were performed to determine the physicochemical properties of quercetin-succinic acid co-crystals. Dissolution was studied in medium citrate buffer with 2% SLS for 60 min using USP II (paddle) apparatus at 100 rpm and 37°C. Results: Based on diffractogram, thermogram, infrared spectrum, and microscopic capture, the physicochemical properties of quercetin-succinic acid co-crystals showed difference to those of quercetin. In addition, the in vitro dissolution test showed that the dissolution profile of co-crystals was significantly higher than pure quercetin. Conclusion: This study suggests that the formation of quercetin-succinic acid co-crystals using solvent evaporation enhanced the physicochemical properties and dissolution rate of quercetin. ABSTRACT

Objective: The aim of the present study was to obtain raw quercetin materials using solid dispersion (SD) system with higher solubility and dissolution rate than pure quercetin. Materials and Methods: The SD of quercetin-hydroxypropyl methyl cellulose (HPMC) was prepared by solvent method. Subsequently, the SD was tested for its solubility and in vitro dissolution. The physicochemical properties were characterized by powder X-ray diffractometer, differential thermal analyzer, FT-infrared spectrophotometer, and scanning electron microscope. Results: Solubility test, dissolution test, and physicochemical property characterization on the SD of Quercetin-HPMC were then compared to pure quercetin and the physical mixture. Based on the results of one-way analysis of variance test, α = 0.05 indicated a significant difference in the solubility and dissolution rate. Conclusions: Quercetin-HPMC SD was in substance which resulted in the increase of solubility and dissolution rate. These findings may enhance bioavailability to increase drug efficacy.

Objective: The present study aims to prepare and characterize cocrystals of artesunate (AR)-nicotinamide (NI) in order to improve bioavailability and efficacy of artesunate as an antimalarial drug. Methods: Cocrystals were prepared using solvent evaporation and slurry methods. Physicochemical characterizations were performed using Hot Stage Microscope (HSM), infrared spectroscopy (IR), thermal analysis DTA, Powder X-Ray Diffraction (PXRD) and Scanning Electron Microscope (SEM). Results: The study revealed that re-crystallization of AR, NI and a physical mixture of both compounds showed distinctive shapes as shown by HSM microscope. AR has a needle shape, whereas NI showed mosaic spherulite crystal. Furthermore, as the two compounds experienced a contact one another, new crystals i.e. fiber-like shape were observed, indicating formation of a cocrystal of AR-NI was successfully achieved. Two different molar ratios of AR-NI from the phase diagram (i.e. 50:50 and 60:40 %) showed a decrease in the melting temperature i.e. 104.0C and 104.7C, respectively, in comparison with the melting point of the constituent materials (AR 133.6C and NI 142.2C). PXRD diffractogram showed that cocrystal of AR–NI exhibited new diffraction peaks at 2 = 5.8; 17.4 and 17.8, whereas no peaks were found for physical mixtures of AR-NI. Characterization with IR showed disappearance of transmission peaks at 2976 and 2639 cm-1 indicating a loss of NH 3+ bending bands. Furthermore, disappearance of C=O stretch at 1346 cm-1 and-OH bending at 1485 cm-1 indicated a formation of hydrogen bonding between AR and NI. This was due to the formation of cocrystals prepared by solvent evaporation method, since the cocrystals made by the slurry method only showed the loss of NH3 + at 2639 cm-1. SEM micrographs showed that cocrystals prepared by solvent method have a more homogeneous mixture of AR-NI compared to the cocrystal formed by slurry method. Conclusion: The study concludes that cocrystals of AR-NI were successfully formed using solvent evaporation and slurry methods. The formed co-crystals of AR-NI exhibited different physicochemical characteristics as compared to the constituent materials. The formed cocrystals prepared by solvent evaporation method have a lower melting point and relatively more homogeneous in terms of crystal composition.

ABSTRACT Objective: The aims of this study was to investigate the solubility, dissolution rate and antimalarial activity against Plasmodium berghei of artesunate (AR)-nicotinamide co-crystal prepared by solvent evaporation (CoSE) and slurry (CoS) method. Methods: Co-crystals of AR-nicotinamide prepared by solvent evaporation and slurry methods were tested for solubility, dissolution rate and activity of antimalarial compared to pure AR and physical mixture (PM) of AR and nicotinamide. Solubility test was conducted in distilled water at 37±0.5°C and dissolution test was done in distilled water medium at 37±0.5°C using paddle stirrer. Antimalarial activity test was carried out on female mice infected by P. berghei then parasitemia was observed. Results: The AR solubility of slightly increased from 1236.66±141.42 to 1368.46±49.17 mg/L. Dissolution data at 30 minutes respectively for AR, PM, CoS and CoSE (76.51±14.93; 75.45±18.07; 85.14±12.94 and 123.24±7.68%). The results were antimala...

Objectives: The aim of this study was to investigate crystallinity and compatibility transformation of two binary mixtures of analgesic substance with excipient due to mixing and compression. Methods: Analgesic substances used in this study were mefenamic acid (MA) and acetaminophen (AC). Each substance was mixed with microcrystalline selolusa as excipient with drug-excipient ratio of 70:30, 80:20 and 90:10 %w/w then compressed with pressure of 29.4 kN. Characterization was done by Powder X-Ray Diffraction (PXRD), thermal analysis (DTA), FTIR spectrometer and a Scanning Electron Microscope (SEM). Mechanical properties was also evaluated by calculating its tensile strength Results: Evaluation of crystallites size of MA and MA-MCC mixture showed that the value of MA crystallite size is relatively fixed in all the peaks observed. Crystallite size of the AC and AC-MCC mixture also showed similar results with MA. From the elastic modulus curve, it was recognized that the tensile strength of MA is greater than AC, it indicates that the MA is more plastic than AC. Conclution: X-ray powder diffraction of binary mixture indicated that intensity of both MA and AC decreased with increasing amount of MCC. The average crystallite size were 15-19 Å (MA) and 21-30 Å (AC). It was known that MA has compactibility better than AC.

Objective: The objective of this research was to enhance the dissolution characteristic of diterpene lactone fraction of Andrographis paniculata Nees (DTLF) containing 75.9% andrographolide. The effect of carboxymethyl chitosan concentration on physical characteristics, entrapment efficiency and in vitro release of diterpene lactone fraction of Andrographis paniculata Nees (DTLF) particulate system were investigated. Methods : Diterpene lactone fraction of Andrographis paniculata Nees (DTLF) particulate system with different amount of carboxymethyl chitosan (CMChi) were prepared by ionic gelation followed by spray drying methods with CaCl 2 as cross linker. The particles were evaluated in terms of physical state, drug entrapment efficiency and in vitro release rate. R e s u l t s : T h e r e s u l t s h o w e d t h a t D T L F i s a l r e a d y e n t r a p p e d i n t h e s y s t e m h e n c e t h e crystallinity reduced. The entrapment efficiency increases with increasing the amount of carboxymethyl chitosan, between 84% up to 90%. The release rate of the particles in 0.5% SLS media were 1.5 times higher than DTL substance, but not significantly different as the polymer amount increased. Conclusion : Entrapment of DTL in CMChi particulates system could reduce the crystallinity. Hence DTL – CMChi particles were able to enhance release rate of DTL up to 1.5 times.