Characterization and Prediction of the Non-Bonded Molecular Interactions between Racemic Ibuprofen and α-Lactose Monohydrate Crystals Produced from Melt Granulation and Slow Evaporation Crystallization

Zulfahmi Lukman; Nornizar Anuar; Noor Fitrah Abu Bakar; Norazah Abdul Rahman

doi:10.22146/ijc.48912

Characterization and Prediction of the Non-Bonded Molecular Interactions between Racemic Ibuprofen and α-Lactose Monohydrate Crystals Produced from Melt Granulation and Slow Evaporation Crystallization

https://doi.org/10.22146/ijc.48912

Zulfahmi Lukman⁽¹⁾, Nornizar Anuar^(2*), Noor Fitrah Abu Bakar⁽³⁾, Norazah Abdul Rahman⁽⁴⁾

(1) Faculty of Chemical Engineering, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
(2) Faculty of Chemical Engineering, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
(3) Faculty of Chemical Engineering, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
(4) Faculty of Chemical Engineering, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
(*) Corresponding Author

Abstract

Granulation of racemic ibuprofen (±IBP) and α-lactose monohydrate (ALM) at a slightly lower (±IBP) melting point is an efficient method of binding the active pharmaceutical ingredients (API) and excipient in a binderless condition. However, the co-crystals may be formed from recrystallization of ±IBP on ALM. The objective of this study is to evaluate the tendency of co-crystal formation of granules (3:7 w/w ratio of ±IBP:ALM) by melt granulation process. Second, investigate the recovery of crystals from polyethylene glycol (PEG) 300 solutions containing ±IBP-ALM mixtures. Characterizations of the samples were performed using Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC) and Powder X-Ray Diffraction (PXRD) system of the ±IBP-ALM granules produced from melt crystallization and harvested crystals from PEG 300 solution which is produced using slow evaporation crystallization. Crystal analysis of solution containing ±IBP-ALM mixtures revealed that the crystals formed were not co-crystals. Molecular interactions assessment through binding prediction between ±IBP and ALM terminating surfaces was conducted using molecular modelling technique. The result showed that the favorable binding sites of ±IBP molecules were on the surfaces of (0-20), (1-10), (001) and (011) ALM crystals. Successful binding prediction by the attachment energy method has proven that the co-crystal formation between these molecules is theoretically possible.

Keywords

surface chemistry; hydrogen bond; lattice energy; melt crystallization; binding prediction

Full Text:

Full Text PDF

References

[1] Pauli-Bruns, A., Knop, K., and Lippold, B.C., 2010, Preparation of sustained release matrix pellets by melt agglomeration in the fluidized bed: Influence of formulation variables and modelling of agglomerate growth, Eur. J. Pharm. Biopharm., 74 (3), 503–512.

[2] Vilhelmsen, T., Eliasen, H., and Schaefer, T., 2005, Effect of a melt agglomeration process on agglomerates containing solid dispersions, Int. J. Pharm., 303(1-2), 132–142.

[3] Yang, D., Kulkarni, R., Behme, R.J., and Kotiyan, P.N., 2007, Effect of the melt granulation technique on the dissolution characteristics of griseofulvin, Int. J. Pharm., 329 (1-2), 72–80.

[4] Ab Ghani, S., Abu Bakar, N.F., Abu Bakar, M.R., Yusof, Y.A., and Abd Rahman, N., 2018, Granulation of mefenamic acid and poly-ethylene glycol (PEG) using pressure swing granulation (PSG) technique in fluidized bed, Malays. J. Anal. Sci., 22 (2), 318–325.

[5] Walker, G.M., Bell, S.E.J., Andrews, G., and Jones, D., 2007, Co-melt fluidized bed granulation of pharmaceutical powders: Improvements in drug bioavailability, Chem. Eng. Sci., 62 (1-2), 451–462.

[6] Walker, G.M., Andrews, G., and Jones, D., 2006, Effect of process parameters on the melt granulation of pharmaceutical powders, Powder Technol., 65 (3), 161–166.

[7] Ghorab, M.K., and Adeyeye, M.C., 2001, Enhancement of ibuprofen dissolution via wet granulation with β-cyclodextrin, Pharm. Dev. Technol., 6 (3), 305–314.

[8] Pacheco, D.P., Manrique, Y.J., and Martínez, F., 2007, Thermodynamic study of the solubility of ibuprofen and naproxen in some ethanol + propylene glycol mixtures, Fluid Phase Equilib., 262 (1-2), 23–31.

[9] Passerini, N., Albertini, B., González-Rodríguez, M.L., Cavallari, C., and Rodriguez, L., 2002, Preparation and characterization of ibuprofen-poloxamer 188 granules obtained by melt granulation, Eur. J. Pharm. Sci., 15 (1), 71–78.

[10] Abu Bakar, N.F., Mujumdar, A., Urabe, S., Takano, K., Nishii, K., and Horio, M., 2007, Improvement of sticking tendency of granules during tabletting process by pressure swing granulation, Powder Technol., 176 (2-3), 137–147.

[11] Perlovich, G.L., Kurkov, S.V., Hansen, L.K., and Bauer-Brandl, A., 2004, Thermodynamics of sublimation, crystal lattice energies, and crystal structures of racemates and enantiomers: (+) and (±)-ibuprofen, J. Pharm. Sci., 93 (3), 654–666.

[12] Mameri, F., Koutchoukali, O., Bouhelassa, M., Hartwig, A., Nemdili, L., and Ulrich, J., 2017, The feasibility of coating by cooling crystallization on ibuprofen naked tablets, Front. Chem. Sci. Eng., 11, 211–219.

[13] Myerson, A.S., 2002, Handbook of Industrial Crystallization, 2^nd Ed., Butterworth-Heinemann, Boston, 312.

[14] Chen, J., Sarma, B., Evans, J.M.B., and Myerson, A.S., 2011, Pharmaceutical crystallization, Cryst. Growth Des., 11 (4), 887–895.

[15] Stahly, G.P., 2007, Diversity in single- and multiple-component crystals. The search for and prevalence of polymorphs and cocrystals, Cryst. Growth Des., 7 (6), 1007–1026.

[16] Dhumal, R.S., Kelly, A.L., York, P., Coates, P.D., and Paradkar, A., 2010, Cocrystalization and simultaneous agglomeration using hot melt extrusion, Pharm. Res., 27 (12), 2725–2733.

[17] Rasenack, N., and Müller, B.W., 2002, Ibuprofen crystals with optimized properties, Int. J. Pharm., 245 (1-2), 9–24.

[18] Alshahateet, S.F., 2011, Synthesis and X-ray crystallographic analysis of pharmaceutical model rac-ibuprofen cocrystal, J. Chem. Crystallogr., 41, 276–279.

[19] Berry, D.J., Seaton, C.C., Clegg, W., Harrington, R.W., Coles, S.J., Horton, P.N., Hursthouse, M.B., Storey, R., Jones, W., Friščić, T., and Blagden, N., 2008, Applying hot-stage microscopy to co-crystal screening: A study of nicotinamide with seven active pharmaceutical ingredients, Cryst. Growth Des., 8 (5), 1697–1712.

[20] Rajanikant, P., Nirav, P., Patel, N.M., and Patel, M.M., 2010, A novel approach for dissolution enhancement of Ibuprofen by preparing floating granules, Int. J. Res. Pharm. Sci., 1 (1), 57–64.

[21] Chan, K.L.A., and Kazarian, S.G., 2006, High-throughput study of poly(ethylene glycol)/ibuprofen formulations under controlled environment using FTIR imaging, J. Comb. Chem., 8 (1), 26–31.

[22] Hammond, R.B., Pencheva, K., Ramachandran, V., and Roberts, K.J., 2007, Application of grid-based molecular methods for modeling solvent-dependent crystal growth morphology: Aspirin crystallized from aqueous ethanolic solution, Cryst. Growth Des., 7 (9), 1571–1574.

[23] Anuar, N., Daud, W.R.W., Roberts, K.J., Kamarudin, S.K., and Tasirin, S.M., 2012, Morphology and associated surface chemistry of L-isoleucine crystals modeled under the influence of L-leucine additive molecules, Cryst. Growth Des., 12 (5), 2195–2203.

[24] Rosbottom, I., Ma, C.Y., Turner, T.D., O’Connell, R.A., Loughrey, J., Sadiq, G., Davey, R.J., and Roberts, K.J., 2017, Influence of solvent composition on the crystal morphology and structure of p‑aminobenzoic acid crystallized from mixed ethanol and nitromethane solutions, Cryst. Growth Des., 17 (8), 4151–4161.

[25] Abdul Mudalip, S.K., Adam, F., and Abu Bakar, M.R., 2019, Evaluation of the intermolecular interactions and polymorphism of mefenamic acid crystals in N,N-dimethyl formamide solution: A molecular dynamics simulation and experimental study, C.R. Chim., 22 (11-12), 771–778.

[26] Rosbottom, I., Pickering, J.H., Etbon, B., Hammond, R.B., and Roberts, K.J., 2018, Examination of inequivalent wetting on the crystal habit surfaces of RS-ibuprofen using grid-based molecular modelling, Phys. Chem. Chem. Phys., 20 (17), 11622–11633.

[27] Cai, Z., Liu, Y., Song, Y., Guan, G., and Jiang, Y., 2017, The effect of tailor-made additives on crystal growth of methyl paraben: Experiments and modelling, J. Cryst. Growth, 461, 1–9.

[28] Wu, H., Wang, J., Li, F., Liu, Q., Zong, S., Bi, J., Wang, N., Shan, G., and Hao, H., 2019, Investigations on growth intensification of p-toluamide crystals based on growth rate analysis and molecular simulation, CrystEngComm, 21 (36), 5519–5525.

[29] Fries, D., Rao, S.T., and Sundaralingam, M., 1971, Structural chemistry of carbohydrates. III. Crystal and molecular dtructure of 4-O-β-D-galactopyranosyl-α-D-glucopyranose monohydrate (α-lactose monohydrate), Acta Crystallogr., Sect. B: Struct. Sci., 27 (5), 994–1005.

[30] Lukman, Z., Anuar, N., Abu Bakar, N.F., and Abd Rahman, N., 2018, Alpha lactose monohydrate morphology: Molecular modelling and experimental approach, Int. J. Eng. Technol., 7 (4.18), 107–112.

[31] Dincer, T.D., Parkinson, G.M., Rohl, A.L., and Ogden, M.I., 1999, Crystallization of α-lactose monohydrate from dimethyl sulfoxide (DMSO) solutions: Influence of β-lactose, J. Cryst. Growth, 205 (3), 368–374.

[32] MacFhionnghaile, P., Svoboda, V., McGinty, J., Nordon, A., and Sefcik, J., 2017, Crystallization diagram for antisolvent crystallization of lactose: Using design of experiments to investigate continuous mixing-induced supersaturation, Cryst. Growth Des., 17 (5), 2611–2621.

[33] Smith, J.H., Dann, S.E., Elsegood, M.R.J., Dale, S.H., and Blatchford, C.G., 2005, α-Lactose monohydrate: A redetermination at 150 K, Acta Crystallogr., Sect. E: Struct. Rep. Online, 61(8), 2499–2501.

[34] Garnier, S., Petit, S., and Coquerel, G., 2002, Influence of supersaturation and structurally related additives on the crystal growth of α-lactose monohydrate, J. Cryst. Growth, 234 (1), 207–219.

[35] Bisker-Leib, V., and Doherty, M.F., 2001, Modeling the crystal shape of polar organic materials: Prediction of urea crystals grown from polar and nonpolar solvents, Cryst. Growth Des., 1 (6), 455–461.

[36] Dressler, D.H., Hod, I., and Mastai, Y., 2008, Stabilization of α-L-glutamic acid on chiral thin films–A theoretical and experimental study, J. Cryst. Growth, 310 (7-9), 1718–1724.

[37] Poornachary, S.K., Chow, P.S., and Tan, R.B.H., 2008, Impurity effects on the growth of molecular crystals: Experiments and modeling, Adv. Powder Technol., 19 (5), 459–473.

[38] Dwivedi, S.K., Sattari, S., Jamali, F., and Mitchell, A.G., 1992, Ibuprofen racemate and enantiomers: Phase diagram, solubility and thermodynamic studies, Int. J. Pharm., 87 (1-3), 95–104.

[39] Uchida, H., Yoshida, M., Kojima, Y., Yamazoe, Y., and Matsuoka, M., 2005, Measurement and correlation of the solid-liquid-gas equilibria for the carbon dioxide + S-(+)-ibuprofen and carbon dioxide + RS-(±)-ibuprofen systems, J. Chem. Eng. Data, 50 (1), 11–15.

[40] Romero, A.J., Savastano, L., and Rhodes, C., 1993, Monitoring crystal modifications in systems containing ibuprofen, Int. J. Pharm., 99 (2-3), 125–134.

[41] Xu, F., Sun, L.X., Tan, Z.C., Liang, J.G., and Li, R.L., 2004, Thermodynamic study of ibuprofen by adiabatic calorimetry and thermal analysis, Thermochim. Acta, 412 (1-2), 33–57.

[42] Lerdkanchanaporn, S., and Dollimore, D., 1997, A thermal analysis study of ibuprofen, J. Therm. Anal., 49, 879–886.

[43] Lefort, R., Caron, V., Willart, J.F., and Descamps, M., 2006, Mutarotational kinetics and glass transition of lactose, Solid State Commun., 140 (7-8), 329–334.

[44] Gombás, Á., Szabó-Révész, P., Kata, M., Regdon, G.Jr., and Erõs, I., 2002, Quantitative determination of crystallinity of α-lactose monohydrate by DSC, J. Therm. Anal. Calorim., 68, 503–510.

[45] Listiohadi, Y., Hourigan, J.A., Sleigh, R.W., and Steele, R.J., 2008, Moisture sorption, compressibility and caking of lactose polymorphs, Int. J. Pharm., 359 (1-2), 123–134.

[46] Genina, N., Räikkönen, H., Heinämäki, J., Antikainen, O., Siiriä, S., Veski, P., and Yliruusi, J., 2009, Effective modification of particle surface properties using ultrasonic water mist, AAPS PharmSciTech, 10 (1), 282–288.

[47] Kaialy, W., Martin, G.P., Ticehurst, M.D., Royall, P., Mohammad, M.A., Murphy, J., and Nokhodchi, A., 2011, Characterisation and deposition studies of recrystallised lactose from binary mixtures of ethanol/butanol for improved drug delivery from dry powder inhalers, AAPS J., 13 (1), 30–43.

[48] Raut, D.M., Allada, R., Pavan, K.V., Deshpande, G., Patil, D., Patil, A., Deshmukh, A., Raut, D.M., Sakharkar, D.M., Bodke, P.S., and Mahajan, D.T., 2011, Dehydration of lactose monohydrate: Analytical and physical characterization, Der Pharm. Lett., 3 (5), 202–212.

[49] Perissutti, B., Rubessa, F., Moneghini, M., and Voinovich, D., 2003, Formulation design of carbamazepine fast-release tablets prepared by melt granulation technique, Int. J. Pharm., 256 (1-2), 53–63.

[50] Garnier, S., Petit, S., and Coquerel, G., 2002, Dehydration mechanism and crystallization behaviour of lactose, J. Therm. Anal. Calorim., 68, 489–502.

[51] Dhumal, R.S., Biradar, S.V., Paradkar, A.R., and York, P., 2008, Ultrasound assisted engineering of lactose crystals, Pharm. Res., 25 (12), 2835–2844.

[52] Abd Rahim, S., Tan, C.C., and Ramle, N.A., 2016, Carbamazepine-fumaric acid co-crystal screening using solution based method, MATEC Web Conf., 69, 03003.

[53] Othman, M.F., Jamburi, N., Anuar, N., Abd Rahim, S., and Rohalim, N.H., 2016, Ibuprofen-amino acids co-crystal screening via co-grinding methods, MATEC Web Conf., 69, 03002.

[54] Mohammad, M.A., Alhalaweh, A., and Velaga, S.P., 2011, Hansen solubility parameter as a tool to predict cocrystal formation, Int. J. Pharm., 407 (1-2), 63–71.

[55] Greenhalgh, D.J., Williams, A.C., Timmins, P., and York, P., 1999, Solubility parameters as predictors of miscibility in solid dispersions, J. Pharm. Sci., 88 (11), 1182–1190.

DOI: https://doi.org/10.22146/ijc.48912