5ème Séminaire Maghrébin sur les Sciences et les Technologies du Séchage (SMSTS'2015) Ouargla (Algérie), du 22 au 24 Novembre, 2015
Effect of drying technic (spray/freeze/vacuum drying) on stability of cyclodextrin-drug inclusion complex prepared in aqueous solution: case study Gliclazide-Hydroxypropyl-β-cyclodextrin inclusion complex. NAIT BACHIR YACINE, HADJ-ZIANE-ZAFOUR AMEL. Chemical engineering laboratory, process engineering department, faculty of technology, university of Blida 1, soumaa, Blida, Algeria.
[email protected] Abstract: Through the years, β-cyclodextrins have been used in order to increase the solubility of insoluble drugs in water. The first step of this work was to improve the solubility of Gliclazide (GLC), one of the sulfonylurea used for treatment of type 2 diabetes. Inclusion complex of GLC in hydroxypropyl β-cyclodextrin (HPBCD) is prepared with aqueous solution method, with stoichiometric molar ratio 1:1. The aim of the present work was to recuperate solid GLC-HPBC inclusion complex used three different drying technics, spray drying, freeze drying and vacuum drying. Drug content estimation found that spray drying is the best one of them. Characterizations of inclusion complex were carried out by the Fourier transform infrared spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-rays diffraction (XRD); these studies indicated the inclusion of GLC in the cavity of HPBC. KEYWORDS: Spray drying, Freeze drying and Vacuum drying, Gliclazide, hydroxypropyl β-cyclodextrin, inclusion complex, in-vitro dissolution study and Drug content estimation.
1. Formulation of GLIC-HPBCD complex in aqueous solution : 1.1.1. Preparation of HPBCD solution: The solution is prepared by 30 minutes stirring at room temperature of 45 g of HPBCD on 100 ml of water [1]. 1.1.2. Preparation of inclusion complex: GLC with HPBCD in 1:1 molar ratios were taken .GLIM was dissolved in aliquots of ethanol [7,8,9], then the solution of HPBCD was added, after sonication the new solution obtained was shaken for 3 days at room temperature on a rotary flask shaker [2].
2. Drying and recuperation of solid GLC-HPBC inclusion complex: 2.1. Spray drying: The solution is dried using BUCHI Mini Spray Dryer B-290 in standard operation conditions. The inclusion complex code is SD-IC given in table 1.
2.2. Freeze-drying: The solution is frozen by immersion in liquid nitrogen and freeze-dried over 24 hours in a FREEZE-DRYER Cryodos apparatus15. The inclusion complex code is FD-IC given in table 1.
2.3. Vacuum drying: The solution is dried using oven under vacuum type Thermo Scientific. The inclusion complex code is VD-IC given in table 1.
3. Drug Content Estimation:
50 mg of complex was accurately weighed and transferred to 50 ml of volumetric flask and volume was made up to the mark with methanol. From this 1mL was taken in 10 mL volumetric flask and the volume is adjusted up to the mark with same solvent [3] . The absorbance of the solution was measured at 228 nm. The drug content of GLC was calculated using calibration curve data. The data is given in table 1 and show in figure 1.
Table 1: Drug content for all formulations. GLIC:HPBCD ratio drying technic 1:1 Spray drying 1:1 Freeze drying 1:1 Vacuum drying
code formulation SD-IC FD-IC VD-IC
% Drug Content 99.9994 99.2707 97.4622
Figure 1: The drug content of GLC formulations. 4.
Characterization of inclusion complexes:
4.1. FTIR Spectroscopy: The FTIR spectra of GLC and its complex were obtained by Tensor 27 FT-IR spectrophotometer. The powder is deposited directly between the two crystals [4] . FTIR Spectra of pure drug, HPBCD and inclusion complex dried with spray drying method, results shown in fig 2,3and 5, respectively. 1541 1666 N-C=O 2.6
Absorban ce
1700 C=O 2.4 N-H 3287;3374 2.2
2 4000
3000
2000
1000
Wavenumber cm-1
Figure 2: FTIR SPECTRA OF PURE DRUG GLC
2.6
Absorban ce
2.4 1149 C-O 3323 2.2
2 3000
2000
1000
Waven u mber (cm-1)
Figure 3: FTIR SPECTRA OF HPBCD 1528
2.6
1620 N-C=O
Absorbance
2.4 N-H 3 366;3308
2.2
1158 C-O
1716 C=O
3302
2 3000
2000
1000
Wavenumber (cm-1)
Figure 4: FTIR SPECTRA OF GLC-HPBCD INCLUSION COMPLEX (SD-IC)
4.2. Simultaneous TGA-DSC Thermal Analysis: The water content of GLC complex with HPBCD is determined using ThermoGravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) over a temperature range from 10°C to 300°C. The TG-DSC was carried out using a STA 409 PC: ATD; ATG; DSC (1500°C) - NETSCH instrument under a dynamic N2 purging gas atmosphere at a constant rate of 50 cc/min and a heating rate of 5°C/min [5] . DSC and TGA thermograms of GLC and SD-IC were shown in Figure 5 and 6 respectively.
Figure 5: DSC and TGA thermogrames of GLC
Figure 6: DSC and TGA thermograms of GLC-HPBCD inclusion complex.
4.3. X-ray diffractometry: X-ray diffraction patterns of GLC and GLC-HPBCD complex were obtained using a Philips PW 3710 X-ray Diffractometer equipped with X powder. The tube operated at 45 kV, 9 mA [6] . The powder X-ray diffraction patterns of GLC and GLC-HPBCD shown in figure 7 and 8 respectively.
Figure 7: X-ray diffraction of glimepiride (GLIM)
Figure 8: X-ray diffraction of SD-IC.
CONCLUSION: The cyclodextrins like HPBCD can be used to prepare inclusion complexes of GLC with improved solubility of the drug in aqueous solution, and the solid inclusion complex can be recuperated with tree different technics, spray drying, freeze drying and vacuum drying. GLC formed inclusion complex with HPBCD in 1:1 M ratio which show the highest drug content estimation using Spray drying method. FTIR, TG-DSC and XRD analysis confirme clearly the dormation of GLC-HPBCD inclusion complex.
REFERENCES:
[1] E.M.Martin Del Valle, Cyclodextrins and their uses: a review, Process Biochemistry Volume 39, Issue 9, 31 May 2004, Pages 1033–1046. [2] R.Ouarezki; M.H.Guermouche, Preparation, Characterization and Dissolution Test of an Inclusion Complex of Atorvastatin in β-Cyclodextrin Letters in Drug Design & Discovery, Volume 10, Number 4, May 2013 , pp. 289-296(8). [3] J.R.Moyano, T.Ventriglia, J.M.Gines, et al, Study of glimepiride-β-cyclodextrin complex, Boll Chim Farm 2003; 142: 390-395. [4] C.S.Winters, P.York, P.Timmins, 1997, Solid state examination of a gliclazide:beta-cyclodextrin complex, Eur. J. Pharm. Sci. 5, 209–214. [5] K.Uekema, Y.Horiuchi, M.Kikuchi, et al, Enhanced dissolution and oral bioavailability of α-tocopheryl esters by dimethyl-β-cyclodextrin complexation, J Incl. Phenom 1988; 6: 167-1748. [6]J.A.Ryan, 1986, Compressed pellet X-ray diffraction monitoring for optimization of crystallinity in lyophlilized solids: imipenem:cilastatin sodium case. J. Pharm. Sci. 75, 805–807. [7] Nait bachir, Y., Oannoughi, N., & Daoud, K. (2013). Formulation, characterization and in-vitro dissolution study of Glimeperide, b-cyclodextrins inclusion complexes and water soluble polymers ternary systems. Int J Pharm Bio Sci, 4(4). [8] NP Sapkal, VA Kilor, KP Bhusari and AS Daud. Evaluation of some Methods for Preparing Gliclazide- βCyclodextrin Inclusion Complexes. Trop J Pharm Res, December 2007; 6 (4). [9] Ouarezki, Radia; Guermouche, Moulay-Hassane. Preparation, Characterization and Dissolution Test of an Inclusion Complex of Atorvastatin in β-Cyclodextrin. Letters in Drug Design & Discovery, Volume 10, Number 4, 1 May 2013, pp. 289-296(8).
