Formulation Development of a Carrageenan Based Delivery System for Buccal Drug Delivery Using Ibuprofen as a Model Drug

Farnoosh Kianfar, Milan D. Antonijevic, Babur Z. Chowdhry, Joshua S. Boateng

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DOI: 10.4236/jbnb.2011.225070                

Abstract

Solvent cast films are used as oral strips with potential to adhere to the mucosal surface, hydrate and deliver drugs across the buccal membrane. The objective of this study was the formulation development of bioadhesive films with optimum drug loading for buccal delivery. Films prepared from κ-carrageenan, poloxamer and polyethylene glycol or glycerol, were loaded with ibuprofen as a model water insoluble drug. The films were characterized using texture analysis (TA), hot stage microscopy (HSM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), x-ray powder diffraction (XRPD), high performance liquid chromatography (HPLC) and in vitro drug dissolution. Optimized films were obtained from aqueous gels containing 2.5% w/w κ-carrageenan 911, 4% w/w poloxamer 407 and polyethylene glycol (PEG) 600 [5.5% w/w (non-drug loaded) and 6.5% w/w (drug loaded)]. A maximum of 0.8% w/w ibuprofen could be incorporated into the gels to obtain films with optimum characteristics. Texture analysis confirmed that optimum film flexibility was achieved from 5.5% w/w and 6.5% (w/w) of PEG 600 for blank films and ibuprofen loaded films respectively. TGA showed residual water content of the films as approximately 5%. DSC revealed a T_g for ibuprofen at -53.87^。C, a unified T_m for PEG 600/poloxamer mixture at 32.74^。C and the existence of ibuprofen in amorphous form, and confirmed by XRPD. Drug dissolution at a pH simulating that of saliva showed that amorphous ibuprofen was released from the films at a faster rate than the pure crystalline drug. The results show successful design of a carrageenan and poloxamer based drug delivery system with potential for buccal drug delivery and showed the conversion of crystalline ibuprofen to the amorphous form during film formation.

Keywords

Carrageenan, Drug Dissolution, Physical Characterization, Plasticizer, Poloxamer

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	A. Liekweg, M. Westfeld and U. Jaehde, “From Oncology Pharmacy to Pharmaceutical Care: New Contributions to Multidisciplinary Cancer Care,” Supplementary Care in Cancer, Vol. 12, No. 2, 2004, pp. 73-79. doi:10.1007/s00520-003-0539-4
[2]	M. Werle, A. Makhlof and H. Takeuchi, “Oral Protein Delivery: A Patent Review of Academic and Industrial Approaches,” Recent Patent in Drug Delivery Formulations, Vol. 3, No. 2, 2009, pp. 94-104. doi:10.2174/187221109788452221
[3]	D. K. Pettit and W. R. Gombotz, “The Development of Site-Specific Drug-Delivery Systems for Protein and Peptide Biopharmaceuticals,” Trends in Biotechnology, Vol. 16, No. 8, 1998, pp. 343-349. doi:10.1016/S0167-7799(98)01186-X
[4]	J. K. Oh, R. Drumright, D. Siegwart and K. Maty-jaszewski, “The Development of Microgels/Nanogels for Drug Delivery Applications,” Progress in Polymer Science, Vol. 33, No. 4, 2008, pp. 448-477. doi:10.1016/j.progpolymsci.2008.01.002
[5]	K. K. Peh and C. F. Wong, “Polymeric Films as Vehicle for Buccal Delivery: Swelling, Mechanical, and Bioadhesive Properties,” Journal of Pharmacy and Pharmaceutical Science, Vol. 2, 1999, pp. 53-61.
[6]	J. S. Boateng, A. D. Auffret, K. H. Matthews, M. J. Humphrey, H. N. E. Stevens and G. M. Eccleston, “Characterization of Freeze-Dried Wafers and Solvent Evaporated Films as Potential Drug Delivery Systems to Mucosal Surfaces,” International Journal of Pharmaceutics, Vol. 389, No. 1-2, 2010, pp. 24-31. doi:10.1016/j.ijpharm.2010.01.008
[7]	N. Salamat-Miller, M. Chittchang and T. P. Johnston, “The Use of Mucoadhesive Polymers in Buccal Drug Delivery,” Advanced Drug Delivery Reviews, Vol. 57, No. 11, 2005, pp. 1666-1691. doi:10.1016/j.addr.2005.07.003
[8]	S. I. Pather, M. J. Rathbone and S. Senel, “Current Status and the Future of Buccal Drug Delivery Systems,” Expert Opinions in Drug Delivery, Vol. 5, No. 5, 2008, pp. 531- 542. doi:10.1517/17425247.5.5.531
[9]	B. Baert, E. Deconinck, M. Van Gele, M. Slodicka, P. Stoppie, S. Bodé, G. Slegers, Y. Vander Heyden, J. Lambert, J. Beetens and B. De Spiegeleer, “Transdermal Penetration Behavior of Drugs: CART-Clustering, QSPR and Selection of Model Compounds,” Bioorganic Medicinal Chemistry, Vol. 15, No. 22, 2007, pp. 6943-6455. doi:10.1016/j.bmc.2007.07.050
[10]	Y. Yuguchi, T. Thuy, H. Urakawa and K. Kajiwara, “Structural Characteristics of Carrageenan Gels: Temperature and Concentration Dependence,” Food Hydrocolloids, Vol. 16, No. 6, 2002, pp. 515-522. doi:10.1016/S0268-005X(01)00131-X
[11]	O. Tari, S. Kara and O. Pekcan, “Critical Exponents of Kappa Carrageenan in the Coil-Helix and Helix-Coil Hysteresis Loops,” Journal of Macromolecular Science Part B-Physics, Vol. 48, No. 4, 2009, pp. 812-822. doi:10.1080/00222340902956129
[12]	M. Thommes and P. Kleinebudde, “Use of Kappa-Carrageenan as Alternative Pelletisation Aid to Microcrystalline Cellulose in Extrusion/Spheronization. II. Influence of Drug and Filler Type,” European Journal of Pharmaceutics and Biopharmaceutics, Vol. 63, No. 1, 2006. pp. 68-75. doi:10.1016/j.ejpb.2005.10.003
[13]	Y. Liu, W. L. Lu, H. C. Wang, X. Zhang, H. Zhang, X. Q. Wang, T. Y. Zhou and Q. Zhang, “Controlled Delivery of Recombinant Hirudin Based on Thermo-Sensitive Pluronic (R) F127 Hydrogel for Subcutaneous Administration: In Vitro and in Vivo Characterization,” Journal of Controlled Release, Vol. 117, No. 3, 2007, pp. 387-395. doi:10.1016/j.jconrel.2006.11.024
[14]	A. Paavola, J. Yliruusi and P. Rosenberg, “Controlled Release and Dura Mater Permeability of Lidocaine and Ibuprofen from Injectable Poloxamer-Based Gels,” Journal of Controlled Release, Vol. 52, No. 1-2, 1998, pp. 169-178. doi:10.1016/S0168-3659(97)00206-X
[15]	G. G .Z. Zhang, D. Law, E. A. Schmitt and Y. H. Qiu, “Phase Transformation Considerations during Process Development and Manufacture of Solid Oral Dosage Forms,” Advanced Drug Delivery Reviews, Vol. 56, No. 3, 2004, pp. 371-390. doi:10.1016/j.addr.2003.10.009
[16]	F. Tirnaksiz and J. R. Robinson, “Rheological, Mucoad-hesive and Release Properties of Pluronic F-127 Gel and Pluronic F-127/Polycarbophil Mixed Gel Systems,” Pharmazie, Vol. 60, No. 7, 2005, pp. 518-523.
[17]	H. Sohi, A. Ahuja, F. Jalees Ahmad and R. Krishen Khar, “Critical Evaluation of Permeation Enhancers for Oral Mucosal Drug Delivery,” Drug Development and Industrial Pharmacy, Vol. 36, No. 3, 2010, pp. 254-282. doi:10.3109/03639040903117348
[18]	D. Q. M. Craig, “A Review of Thermal Methods Used for the Analysis of the Crystal Form, Solution Thermodynamics and Glass-Transition Behavior of Polyethylene Glycols,” Thermochimica Acta, Vol. 248, 1995, pp. 189- 203. doi:10.1016/0040-6031(94)01886-L
[19]	J. S. Boateng, H. N. E. Stevens, G. M. Eccleston, A. D. Auffret, M. J. Humphrey and K. H. Matthews, “Development and Mechanical Characterization of Solvent-Cast Polymeric Films as Potential Drug Delivery Systems to Mucosal Surfaces,” Drug Development and Industrial Pharmacy, Vol. 35, No. 8, 2009, pp. 986-996. doi:10.1080/03639040902744704
[20]	K. Huynh-Ba, “Handbook of Stability Testing in Pharmaceutical Development: Regulations, Methodologies, and Best Practices,” Springer, 2009, pp. 248-250. doi:10.1007/978-0-387-85627-8
[21]	G. Wypych, “Handbook of Plasticizers,” ChemTec, 2004, pp. 218-220.
[22]	B. C. Hancock and M. Parks, “What Is the True Solubility Advantage for Amorphous Pharmaceuticals?” Pharmaceutical Research, Vol. 17, No. 4, 2000, pp. 397-404. doi:10.1023/A:1007516718048
[23]	L. Yu, “Amorphous pharmaceutical Solids: Preparation, Characterization and Stabilization,” Advanced Drug Delivery Reviews, Vol. 48, No. 1, 2001, pp. 27-42. doi:10.1016/S0169-409X(01)00098-9
[24]	O. K. C. Tsui, T. P. Russel and C. J. Hawker, “Effect of Polymer-Substrate Interactions on the Glass Transition of Polymer Thin Films,” 3rd International Symposium on Slow Dynamics in Complex Systems, Proceedings AIP Conference, Vol. 708, 2004, pp. 598-600.
[25]	S. Farmer, P. Anderson, P. Burns and R. Velagaleti, “Forced Degradation of Ibuprofen in Bulk Drug and Tablets,” Pharmaceutical Technology, Vol. 32, 2002, pp. 28-42.
[26]	W. C. Cory, C. Harris and S. Martinez, “Accelerated Degradation of Ibuprofen in Tablets,” Pharmaceutical Development and Technology, Vol. 15, No. 6, 2010, pp. 636-643. doi:10.3109/10837450903426518
[27]	J. S. Boateng, K. H. Matthews, A. D. Auffret, M. J. Humphrey, H. N. E. Stevens and G. M. Eccleston, “In Vitro Drug Release Studies of Polymeric Freeze-Dried Wafers and Solvent-Cast Films Using Paracetamol as a Model Soluble Drug,” International Journal of Pharmaceutics, Vol. 378, No. 1-2, 2009, pp. 66-72. doi:10.1016/j.ijpharm.2009.05.038
[28]	J. Siepmann and N. A. Peppas, “Modeling of Drug Release from Delivery Systems Based on Hydroxypropyl-methylcellulose (HPMC),” Advanced Drug Delivery Reviews, Vol. 48, No. 2-3, 2001, pp. 139-157. doi:10.1016/S0169-409X(01)00112-0