A New Crystal Engineering Technique for Dissolution Enhancement of Poorly Soluble Drugs Combining Quasi-emulsion and Crystallo-co Agglomeration Methods

Document Type : Research article

Authors

1 Department of Pharmaceutics, Faculty of Pharmacy, Ahram Canadian University, Egypt.

2 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.

3 Department of Pharmaceutics, Faculty of Pharmacy, Egyptian Russian University, Egypt.

Abstract

A target of best dissolution improvement of poorly soluble drugs is a necessity for the success of formulation in industry. The present work describes the preparation, optimization, and evaluation of a new spherical agglomeration technique for glimepiride as a model of poorly soluble drugs. It involved the emulsification of a drug solution containing a dispersed carrier that tailors the crystal habit of the drug to a perfect spherical geometry, in a poor solvent containing a hydrophilic polymer which imparts sphericity and strength to the formed agglomerates. The FTIR peaks of optimized product did not show any sign of chemical interaction between the drug and adsorbed carrier. The DSC and X ray diffractogram showed a peak characteristic of spherical agglomerates with much less intensity than that of glimepiride. The dissolution t1/2 of the drug slightly decreasedfrom 381 min to 334 min in plain agglomerates. Introducing polymers in the aqueous phase of emulsion led to an improvement in the dissolution, reflected in t1/2 ranging from 118 to 231 min. Agglomerates prepared with Starlac/PVP demonstrated the most optimum physicochemical characteristics being spherical, with the best flowability and packability parameters. The t1/2 was as short as 19 min. The new carrier/polymer system offered a synergistic combination that highly contributed in dissolution enhancement of glimepiride. The spheronization and amorphisation offered by the new technique could account for such improvement.

Graphical Abstract

A New Crystal Engineering Technique for Dissolution Enhancement of Poorly Soluble Drugs Combining Quasi-emulsion and Crystallo-co Agglomeration Methods

Keywords

References

(1) Kawabata Y, Wada K, Nakatani M, Yamada S and Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int. J. of Pharm.(2011) 420: 1-10.
(2) Kawakami K. Modification of physicochemical characteristics of active pharmaceutical ingredients and application of supersaturatable dosage forms for improving bioavailability of poorly absorbed drugs. Adv. Drug Deliv. Rev. (2012) 64: 480-495.
(3) Wei H and Lobenberg R. Biorelevant dissolution media as a predictive tool for glyburide a class II drug. Eur. J. of Pharm. Sci. ( 2006) 29: 45-52.
(4) Vo CLN, Park C and Lee B. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur. J. of Pharm. and Biopharm.( 2013) 85: 799-813.
(5) Rane Y, Mashru R, Sankalia M and Sankalia J. Effect of Hydrophilic Swellable Polymers on Dissolution Enhancement of Carbamazepine Solid Dispersions Studied Using Response Surface Methodology. AAPS Pharm.Sci.Tech. (2007) 8:E1- E11.
 (6) Abd-El Bary A, Louis D and Sayed S. Olmesartan medoxomil surface solid dispersion-based orodispersible tablets: formulation and in vitro characterization. J. of Drug Deliv. Sci. & Technol.(2014) 24: 665-672.
(7) Shamma RN and Basha M. Soluplus®: A novel polymeric solubilizer for optimization of Carvedilol solid dispersions: Formulation design and effect of method of preparation. Powder Technol. (2013) 37: 406-414.
(8) Vogt M, Kunath K and Dressman JB. Dissolution improvement of four poorly water soluble drugs by cogrinding with commonly used excipients. Eur. J. of Pharm. and Biopharm.( 2008) 68: 330–337.
(9) Kumar S and Gupta SK. Effect of excipients on dissolution enhancement of aceclofenac solid dispersions studied using response surface methodology: a technical note. Arch. Pharm. Res.( 2014) 37: 340-351.
(10) Chauhan H,  Hui-Gu C and Atef E. Correlating the behaviour of polymers in solution as precipitation inhibitor to its amorphous stabilization ability in solid dispersions. J. Pharm. Sci.(2013) 102: 1924-1935.
(11) Nokhodchi A, Maghsoodi M, Hassan-Zadeh D and Barzegar-Jalali M. Preparation of agglomerated crystals for improving flowability and compactibility of poorly flowable and compactible drugs and excipients. Powder Technol. (2007) 175: 73-81.
(12) Thati J and Rasmuson Ǻ. On the mechanisms of formation of spherical agglomerates. Eur. J. Pharm. Sci. (2011) 42: 365-379.
(13) Junghanns J and Müller R. Nanocrystal technology, drug delivery and clinical applications. Int. J. Nanomedicine (2008) 3: 295-309.
(14) Borislav T, Christina V, Denitsa A, Yordan Y, Kati A, Virginia T, Ivanka S, Daniela K and Krassimira Y. Improvement of dissolution of poorly soluble glimepiride by loading on two types of mesoporous silica carriers J. of Solid state Chem. (2018), https://doi.org/10.1016/j.jssc.2018.12.062
(15) Ribardière A, Tchoreloff P, Couarraze G and Puisieux F. Modification of ketoprofen bead structure produced by the spherical crystallization technique with a two solvent system. Int. J. Pharm. (1996) 144: 195-207.
(16) Katta J and Rasmuson A°.Spherical crystallization of benzoic acid. Int. J. of Pharm. (2008) 348: 61-69.
(17) Viswanathan C, Kulkarni S and Kolwankar D. Spherical agglomeration of mefenamic acid and nabumetone to improve micromeritics and solubility: A Technical Note. AAPS Pharm. Sci. Tech. (2006) 7: E1-E4.
(18) Bhadra S, Kumar M, Jain S, Agrawal S and Agrawal GP. Spherical crystallization of mefenamic acid.  Pharm. Technol. (2004) 2: 66-76.
(19) Amaro-González D and Biscans B. Spherical agglomeration during crystallization of an active pharmaceutical ingredient.  Powder Technol. (2002) 128: 188-194.
(20) Mahanty S, Sruti J, Niranjan Patra Ch and Bhanoji Rao ME. Particle design of drugs by spherical crystallization techniques. Int. J. of Pharm. Sci. and Nanotechnol. (2010) 3: 912-918.
(21) Yadav AV and Yadav VB. Preparation and evaluation of polymeric carbamazepin spherical crystals by emulsion solvent diffusion technique. Asian J. of Pharm. (2009) 3: 18-25.
(22) Fodor-Kardos A, Toth J and Gyenis J. Preparation of protein loaded chitosan microparticles by combined precipitation and spherical agglomeration. Powder Technol. (2013) 244: 16-25.
(23) Garala(a) KC, Patel JM, Dhingani AP and Dharamsi AT. Preparation and evaluation of agglomerated crystals by crystallo-co-agglomeration: An integrated approach of principal component analysis and Box–Behnken experimental design.  Int. J. of Pharm. (2013a) 452: 135-156.
(24) Garala(b) KC, Patel JM, Dhingani AP and Dharamsi AT. Quality by design (QbD) approach for developing agglomerates containing racecadotril and loperamide hydrochloride by crystallo-co-agglomeration.  Powder Technol. (2013b) 247: 128-146.
(25) Maghsoodi M, Taghizadeh O, Martin GP and Nokhodchi A. Particle design of naproxen-disintegrant agglomerates for direct compression by a crystallo-co-agglomeration technique. Powder Technol. (2008) 351: 45-54.
(26) Patil SV and Sahoo SK. Improvement in compressibility, flowability and drug release of glibenclamide by spherical crystallization with additives. Digest J. Nanomater. Biostruct. (2011) 6: 1463-1477.
(27) Carstensen JT. Advanced pharmaceutical solids (2001)  (pp. 302, 311). New York, Basel: Marcel Dekker.
(28) Sinko PJ. Martin’s physical pharmacy and pharmaceutical sciences  (2006) Philadelphia: Lippincott Williams and Wilkins, p. 558.
(29) Wells J. Pharmaceutical preformulation. The physicochemical properties of drug substances (1988) UK: Ellis Horwood Limited, pp. 209–210.
(30) Aulton ME, Aulton’s pharmaceutics: The design and manufacture of medicines (2007) (pp. 176–7, 449-451). Philadelphia: Churchill Livingstone Elsevier.
(31) Kawakita K and Ludde KH. Some considerations on powder compression equations. Powder Technol (1971) 4: 61–68.
(32) Hu R, Zhu J, Chen G, Sun Y, Mei K and Li S. Preparation of sustained-release simvastatin microspheres by spherical crystallization technique. Asian J of Pharm Sci (2006) 1: 47-52.
(33) Paradkar AR, Pawar AP, Chordiya JK, Patil VB and Ketkar AR. Spherical crystallization of  celecoxib.  Drug Dev. Ind. Pharm. (2002) 28: 1213-1220.
(34) Kawashima Y, Okumura M and Takenaka H. Spherical crystallization. Direct spherical agglomeration of salicylic acid crystals during crystallization.  Science (1982)  216: 1127–1128.
(35) Nokhodchi A and Maghsoodi M. Preparation of spherical crystal agglomerates of naproxen containing disintegrant for direct tablet making by spherical crystallization technique.   AAPS Pharm. Sci. Tech. (2008) 9: 54-59.
(36) Bühler V, Polyvinylpyrrolidone Excipients for Pharmaceuticals: Povidone, Crospovidone and Copovidone (2005) (pp. 126-162). Springer-Verlag Berlin: Heidelberg, Germany.
(37) Omidian H and Park K. Swelling agents and devices in oral drug delivery. J. Drug Deliv. Sci. Technol. (2008) 18:  83-93.
(38) Homayouni A , Sadeghi F, Varshosaz J, Garekani  HA, Nokhodchi A. Comparing various techniques to produce micro/nanoparticles for enhancing the dissolution of celecoxib containing PVP. Eur J of Pharm Biopharm (2014) 88: 261–274
(39) Kawashima Y, Imai M, Takeuchi H, Yamamoto H and Kamiya K. Development of agglomerated crystals of ascorbic acid by the spherical crystallization technique for direct tableting, and evaluation of their compactibilities.  Kona (2002) 20:  251-262.
(40) Lopez MEV, Reyes LN, Anguiano S, Otero-Espinar FJ and Méndez JB.  Formulation of triamcinolone acetonide pellets suitable for coating and colon targeting. Int. J. Pharm. (1999) 179: 229- 235.
(41) Iwamoto S, Nakagawa K, Sugiura S and Mitsutoshi Nakajima M.  Preparation of gelatin microbeads with a narrow size distribution using microchannel emulsification. AAPS Pharm. Sci. Tech. (2002) 3: 1-5.
Iranian Journal of Pharmaceutical Research
Volume 19, Issue 2
Spring 2020
Pages 219-235

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