Enhancement of solubility & dissolution rate of Nifedipine by using Novel Solubilizer sepitrap 80 & Sepitrap 4000
The enhancement in solubility and dissolution rate of BCS class-II drug Nifedipine was achieved by simple physical mixture with sepitrap 80 & sepitrap 4000 in 1:1 & 1:2 proportion. The saturation solubility studies shows 263 % & 368 % increase in the solubility in physical mixture of Nifedipine with sepitrap 80 & sepitrap 4000 respectively. The physicochemical properties of pure Nifedipine compared to their physical mixtures with sepitrap 80 & sepitrap 4000 were determined using FTIR, DSC & PXRD. The FTIR and DSC studies shows no any interaction in Nifedipine and sepitrap, the marked broadening and distinct reduction in intensity with shifting of drug endotherm was displayed physical mixture with sepitrap demonstrate positive effect. The PXRD diffractograms shows distinctive peaks but reduction in peak intensity in terms of counts indicating conversion of drug in amorphous forms. The surface morphology of the prepared physical mixture was examined by SEM which indicating no significant change in its surface morphology due to no use any solvent during the preparation of physical mixture . Photostability studies shows that rate of photo degradation is very slow in Physical mixture with sepitrap as compared to pure Nifedipine. Dissolution studies in SGF & SIF shows that significant enhancement by use of novel solubilizer sepitrap 80 as well as sepitrap 4000 in 1:2 proportions. The physical mixture containing sepitrap 4000 was found stable as there was no any significant change in appearance and drug dissolution after three month stability studies.
2] Mitchell S.A., Reynolds T.D., Dasbach T.P.,. A compaction process to enhance dissolution of poorly water-soluble drugs using hydroxypropyl methylcellulose. Int. J. Pharm. 2003; 250:3–11.
3] Sugimoto M., Okagaki T., Narisawa S., Koida Y., Nakajima K., Improvement of dissolution characteristics and bioavailability of poorly water-soluble drugs by novel co grinding method using water-soluble polymer. Int. J. Pharm. 1998; 160:11–19.
4] Suzuki H., Ogawa M., Hironaka K., Ito K., Sunada, H. A nifedipine coground mixture with sodium deoxycholate. II. Dissolution characteristics and stability. Drug. Dev. Ind. Pharm., 2001; 27:951–958.
5] Zajc N., Obreza A., Bele M., Srcic S., Physical properties and dissolution behaviour of nifedipine/mannitol solid dispersions prepared by hot melt method. Int. J. Pharm. 2005; 291:51–58.
6] Yamamura S., Rogers J.A., Characterization and dissolution behavior of Nifedipine and phosphatidyl choline binary systems. Int. J. Pharm. 1996; 130:65–73.
7] Cilurzo F., Minghetti P., Casiraghi A., Montanari L., Characterization of Nifedipine solid dispersions. Int. J. Pharm. 2002; 242:313–317.
8] Portero A., Remunan-Lopez C., Vila-Jato J.L., Effect of chitosan and chitosan glutamate enhancing the dissolution properties of the poorly water soluble drug nifedipine. Int. J. Pharm. 1998; 175: 75–84.
9] Lin C.-W., Cham T.M., Effect of particle size on the available surface area of nifedipine from Nifedipine–polyethylene glycol 6000 solid dispersions. Int. J. Pharm. 1996; 127:261–272.
10] Vippagunta S.R., Maul K.A., Tallavajhala S., Grant, D.J.W., Solid-state characterization of nifedipine solid dispersions. Int. J. Pharm. 2002; 236:111–123.
11] Hirayama F., Wang Z., Uekema K., Effect of 2- hydroxypropyl-beta-cyclodextrin on crystallisation and polymorphic transition of nifedipine in solid state. Pharm. Res. 1994; 111:1766–1770.
12] Ramyasree domala, basanth babu eedara, rajeshri k. Dhurke, Development of Pulsatile Drug Delivery System Using Novel Solubilizers For Antihypertensive Drug, International Journal of Pharmacy and Pharmaceutical Sciences, 2014; 6:659-664
13] Albini A and Fasani E. Photochemistry of Drug: an Overview and Practical Problems. In: Albini A and Fasani E. (Eds.) Drug Photochemistry and Photostability. 1st ed. The Royal Society of Chemistry, Cambridge 1998; 1-65.
14] Majeed IA, Murray WJ, Newton DW, Othman S, and Al-Turk WA. Spectrophotometric study of the photodecomposition kinetics of Nifedipine. J. Pharm. Pharmacol. 1987; 39:1944-1946
15] Dokladalov J, Tykal JA and Coco SJ. Occurrence and measurement of nifidipine and its nitropyridine derivative in human blood plasma. J. Chromatog. 1982; 231:451-458
16] Reddy RK, Veera JM, Mohamed Saleem TS, MadhuSudhana CC. Review on: pulsatile drug delivery systems J Pharm Sci Res, 2009; 4:109-115.
17] Kim EJ, Chun MK, Jang JS, Lee IH, Choi HK. Preparation of a solid dispersion of felodipine using a solvent wetting method Eur J Pharm Biopharm 2006; 64:200-205
18] Won DH, Kim MS, Lee s, Park JS, Hwang SJ. Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation process .Int J Pharm 2005; 301:199-208
19] Swati Changdeo Jagdale,, Vinayak Narhari Jadhav, Aniruddha Rajaram Chabukswar, Bhanudas Shankar Kuchekar, Solubility enhancement, physicochemical characterization and formulation of fast-dissolving tablet of nifedipine-betacyclodextrin complexes, Brazilian Journal of Pharmaceutical Sciences, 2012; 48:131-145
20] Naveen A, katare O, singh B, Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers. Eur. J. Pharm. Biopharm 2007; 65:26-38.
21] Ramana MV, Himaja M, Dua K, A new approach: enhancement of solubility of rofecoxib. Asian J. Pharm., 2008; 2: 96-101.
22] Indian pharmacopoeia Government of India, ministry of health and family welfare’s, published by the controller of publications, The Indian pharmacopoeia commission Ghaziabad. 2007; 3:177-186,447,1442-1445.
23] Jagdale S, kuchekar B, chabukswar A, Musale V, Jadhao M, Preparation and in vitro evaluation of Allopurinol-Gelucire solid dispersions. Int. J. Adv. Pharm. Sci, 2010; 1:60-67.
24] Friedrich H, Nada A, Bodmier R, Solid state and dissolution rate characterization of co-ground mixtures of nifedipine and hydrophillic carriers. Drug Dev. Ind. Pharm., 2005; 31:719-728.
25] Lachman l, Lieberman h a, kaing JL, The theory and practice of industrial pharmacy. 4.ed. New Delhi CBS Publication, 1991
26] Kulkarni G.T, Gowthamarajan K, Suresh B. stability testing of pharmaceutical product: an overview. Indian J Phar Edu 2004; 38:194-202.
27] Papadimitriou SA, Bikiaris D, Avgoustakis K. Microwave-induced enhancement of the dissolution rate of poorly water-soluble tibolone from poly (ethylene glycol) solid dispersions. J Appl Polymer Sci. 2008; 108:1249-1258.
28] Mosab Arafat, Zahaa Ahmed, Momir Mikov, determination of Nifedipine In Rat Plasma Using Hplc-Uv Detector: A Simple Method For Pharmacokinetics And Oral Bioavailability Studies International Journal of Pharmacy and Pharmaceutical Sciences, 2016; 8:98-102
29] Vertzoni MV, Reppas C, Archontaki HA. Sensitive and simple liquid chromatographic method with ultraviolet detection for the determination of nifedipine in canine plasma. Anal Chim Acta 2006; 573-574
30] Thongnopnua P, Viwatwongsa K. Quantitative analysis of Nifedipine in plasma by high-performance liquid chromatography. J Pharm Biomed Anal 1994; 129: 119-25.
31] Grundy JS, Kherani R, Foster RT. Sensitive high-performance liquid chromatographic assay for nifedipine in human plasma utilizing ultraviolet detection. J Chromatogr B: Biomed appl 1994; 654:146-51.
32] International conference on harmonization (ICH) harmonized tripartite guideline for stability testing of new drugs substances and products Q1A (R2) aug-2003. Q1 (R2) Mar 2004.
33] Rhodes CT, Cartesan T. Drug stability principle and procedure, 3rd ed, New York, 2001
34] Yi T, Wan J, Xu H, et al. A new solid self-micro emulsifying formulation prepared by spray-drying to improve the oral bioavailability of poorly water soluble drugs. Eur J Pharm Biopharm 2008; 70:439-444
35] Rogers TL, Johnston KP, Williams III RO. Solution-based particle formation of pharmaceutical powders by supercritical or compressed fluid CO2 and cryogenic spray freezing technologies. Drug Dev Ind Pharm. 2001; 27:1003-1015
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).