1. Introduction Objective Experimental Results and Discussion
ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF CURCUMIN BY EUDRAGIT EPO-BASED SOLID DISPERSIONS PREPARED BY HOT MELT EXTRUSION AND SPRAY DRYING TECHNOLOGY
Avinash B. Gangurde, S.D. Javeer, J.N. Pawar, D. Jaiswar ,Purnima D. Amin
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University under Section 3 of UGC Act- 1956, Elite Status & Centre of Excellence - Govt. of Maharashtra, TEQIP Phase II Funded, Matunga (E), Mumbai – India
Introduction
Curcumin (CUR) is a highly lipophilic drug molecule with a wide range of pharmacological activities. However, its clinical utility is limited due to its poor aqueous solubility and degradation at alkaline pH restricts its oral bioavailability (Anand P. et al., 2007, Yang KY et al., 2007). Therefore, there is need to increase the solubility of curcumin to promote it for oral drug delivery.
Strategies to overcome these problems include conversion of CUR to free flowing micro particles, improving the solubility of curcumin in acidic pH and improving its stability in aqueous media (Paradkar A et al., 2005).
Spray drying (SD) is a technique used for development of micro particulate solid dispersions (SDs) for improving the stability and solubility of compounds (Araujo et al., 2010).
Hot melt extrusion (HME) is a process in which the drug is embedded in polymeric carrier at an elevated temperature and pressure conditions to prepare solid dispersed powder. (Breitenbach et al., 2002).
Cationic polymer (Eudragit EPO) based SDs by using scalable spray drying and hot melt extrusion techniques are the appropriate option for solubility and dissolution rate enhancement of curcumin powder.
Objective
To study the influence of cationic polymer Eudragit EPO on solubility and dissolution rate of poorly water soluble drug curcumin.
The work also involved studying the effect of method of preparation of SDs on the dissolution rate of curcumin
Experimental
SDs of CUR were prepared by varying drug loading 1:0.5, 1:1 and 1:2 ratio as composition shown in Table.
Component
CUR1
CUR2
CUR3
CUR4
CUR5
CUR6
Hot Melt Extrusion (HME)
Spray Drying (SD)
CUR 75 50 35
Eudragit EPO 17
42.5 60
22.5
47.5
62.5
Methocel
2.5
PEG 400 5
---
Acetone
q.s.
Hot Melt Extrusion
Curcumin + Eudragit EPO +PEG 400
Characterizations of SDs- DSC,FTIR,PXRD and SEM study
Enhanced Solubility and dissolution rate
Spray Drying
Results and Discussion
Saturation solubility study
Characterization
DSC
PXRD
In vitro dissolution study
A-Plain CUR
B-CUR6
C-CUR3
The solubility and dissolution rate of CUR was found to be higher in dispersions with higher concentration of Eudragit polymer.
FTIR
SEM
Contact angle measurement
DSC and PXRD revealed that SD prepared by hot melt extrusion and spray drying techniques showed decrease in crystallinity of curcumin when increasing polymer concentration. FTIR study confirmed the stability of drug. SEM study showed uniform spherical shape of spray dried particles and flat broken needles of different sizes, with well-developed edges of hot melt extruded particles.
Samples
SDs
t=0 s
t=60 s
Neat CUR
70±2.42
65±2.12
CUR1
25±1.23
19±1.11
CUR2
18±1.23
14±1.14
CUR3
14±1.19
12±1.15
CUR4
28±1.67
21±1.43
CUR5
20±1.23
15±1.18
CUR6
15±1.23
12±1.18
Conclusion
Eudragit EPO showed a significant increase in solubility and in-vitro release performance of CUR by hot melt extrusion (solubility 3 to 115 µg/ml & dissolution 35 to 64% in 2 hrs.) and spray drying technology (solubility 4 to 125 µg/ml & 30 to 63 % in 2 hrs. The solubility and dissolution rate of CUR was increased by increasing polymer concentration . The conversion of crystalline form of drug in to amorphous form through the formation of solid dispersion, increased dispersibility of drug are the contributing factor for solubility and dissolution rate enhancement.
References
Anand P, Kunnumakkara AB. Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises, Mol Pharm. 4(6), (2007).
Yang KY, Lin LC, Tseng TY, Wang SC, Tsai TH. Oral bioavailability of curcumin in rat and the herbal analysis from curcuma longa by LC-MS/MS J chromatogr B. 853(1-2):183-9 (2007).
1st European Conferences on Pharmaceutics, France , Remis 2015
Authors wish to acknowledge UGC for providing financial support during research work and attending conference.