Reducing ulcerogenic effect of self-nano emulsifying drug delivery system of piroxicam

Iis Wahyuningsih, Wahyu Widyaningsih, Silviana Wulandari

Abstract


Piroxicam is antiinflammatory non-steroidal (AINS) drug group that has anti-inflammatory, analgesic and antipyretic effects. Like most other AINS drugs, piroxicam has low solubility and has gastrointestinal (ulcerogenic) side effects on long-term use. The nano-emulsifying drug delivery system (SNEDDS) is one of the technologies that can be used to overcome it. This study aims to determine the effect of ulcerogenic SNEDDS piroxicam compared with piroxicam formulas instead of SNEDDS. This study uses white rats male strain SD age 2-3 months and weight 100-200 grams of 40 rats. Rats divided into 5 groups. Group I was a normal control group, the test animals were given only water. Group II was a suspending control group treated with a 1% polyvinylpyrrolidone (PVP) solution, group III is a carrier control group treated with SNEDDS carrier which is a mixture of tween 80, virgin coconut oil (VCO) and polyethylene glycol (PEG) 400, group IV was a group of piroxicam drugs suspended with piroxicam 1.08 mg/kg in 1% PVP, group V was treated with SNEDDS piroxicam.Treatment was done for 28 days. After treatment, the gastric of rats were taken to be observed for ulcerogenic effects. Observations were made macroscopically by looking at ulcer scores followed by histopathological observations of tissue. The ulcer score data from each group were analyzed using one-way ANOVAand LSD test. The results showed that the normal control group, 1% PVP suspension and carrier group had a ulcer index of 0.0, 0.0 and 0.0, while the piroxicam suspension group and the SNEDDS group had an ulcer index of 0.88 and 0.0. These results were confirmed by histopathologic results of SNEDDS piroxicam to decrease the effect of pyroxicam ulcerogenic with results in the piroxicam suspension group has ulcer with necrosis by neutrophil infiltration, lymphocytes and mast cells in the mucosal tunica to submucosa. In the SNEDDS piroxicam group there is erosion with necrosis of the mucosal tunica epithelium with infiltration of lymphocytes and mast cells in submucosal tunica. It can be concluded the SNEDDS piroxicam can decrease the ulcerogenic effect.

Keywords


piroxicam, SNEDDS, ulcerogenic

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Anuradha, S.P., Patel, P.A., and Hegde, D., 2013, Peppermint Oil Based Drug Delivery System of Aceclofenac With Improve Anti Inflamatory Activity and Reduced Ulcerogenecity, International Journal of Pharma Bioscience and Technology, 1(2): 89-101.

Balakumar K., Raghavan, C.V., Selvan, N.T., Prasad, R.H., and Abdu, S., 2013, Self Nanoemulsifying Drug Delivery System (SNEDDS) of Rosuvastatin Calcium: Design, Formulation, Bioavailability and Pharmacokinetic Evaluation, Colloids and Surfaces B: Biointerfaces, 112: 337-343.

Bali, V., Ali, M., and Ali, J., 2010, Study of Surfactant Combinations and Development of a Novel Nanoemulsion for Minimising Variations in Bioavailability of Ezetimbe, Colloids Surfaces B: Biointerfaces, 76: 410- 420.

Belhadj, Z., Zhang, S., Zhang, W and Wang, J., 2013, Formulation Development and Bioavailibility Evaluation of Self Nanoemulsifying Drung Delivery System (SNEDDS) of Atorvastatin Calsium, International Journal of Pharmaceutics, 29 (1), 1103-1113.

Blagden, N., de Matas, M.,Gavan, P.T., and York, P., 2007, Crystal Engineering of Active Pharmaceutical Ingredients to Improve Solubility and Dissolution Rates, Adv. Drug Del. Rev., 59(7): 617-630.

Date, A.A., Desai, N., Dixit, R., and Nagarsenker, M., 2010, Self Nanoemulsifying Drug Delivery Systems, Formulation Insights, Applications and Advances, Nanomed, 5:1595–1616.

Dewi, E.C., 2016, Pengembangan Self-Nano Emulsifying Drug Delivery System (SNEDDS) Piroksikam menggunakan Fase Minyak VCO, Skripsi, Fakultas Farmasi Universitas Ahmad Dahlan, Yogyakarta.

Kumar, V., Ramzi, S.C., and Stanley, L.R., 2007, Buku Ajar Patologi, Edisi VII, 627, Penerbit Buku Kedokteran EGC, Jakarta.

Lalwani, J.T., Thakkar, V.T., and Patel, H.V., 2013, Enhancement of Solubility and Oral Bioavailability of Ezetimibe by A Novel Solid Self Nanoemulsifying Drug Delivery System (SNEDDS), International Journal of Pharma Bioscience and Technology, 5(3): 512-553.

Laine, L., Takeuchi, K., and Tarnawski, A., 2008, Gastric Mucosal Defense and Cytoprotection: Bench to Bedside, Gastroenterology, 135 (1): 41–60.

Matsui, H., Shimokawa, O., Kaneko, T., Nagano, Y., Rai, K., and Hyodo, I., 2011, The Pathophysiology of Non-Steroidal Anti-Inflammatory Drug (NSAID) Induced Mucosal Injuries in Stomach and Small Intestine, Journal of Clinical Biochemistry and Nutrition, 48(2):107–111.

Margaretha T, Astarida AGR, Darmawan PNA, Saputri JH, and Yuso IBM, 2011, Penatalaksanaan Gastro- enteropati OAINS di Indonesia. Konsensus Nasional 92(9): 1207-1212.

Mescher, A.L., 2011, Histologi Dasar Junqueira,Edisi 12, 1-3, Diterjemahkan oleh Danny, F., Penerbit Buku Kedokteran EGC,Jakarta.

Nagarsenker, M. S., Meshram, R. N., and Ramprakash, G., 2000, Solid Disper-sion of Hydroxpropyl ß-cyclodextrin and Keterolac: Enhance-ment of In Vitro Dissolution Rates, Improvement in Anti-inflammatory Activity and Reduction in Ulcerogenicity in Rats, Journal of Pharmaceutics and Pharmacology, 52: 949-56.

Nazzal, S., and Khan, M.A., 2002. Response Surface Methodology for Optimazation of Ubiquinone Self Nanoemulsified Drug Delivery System. AAPS Pharm Sci Tech 3(1): 23-31.

Obitte, N.C., Chime, S.A., Ibe, D.C., Nweke, O.R., Ugwudah, T.C., 2013, Piroxicam solid lipid microparticles: in vitro and in vivo evaluation. Am J Pharm Tech Res, 3(3):324–336.

Puspitasari, D.A., 2008, Gambaran Histopatologi Lambung Tikus Putih (Rattus norvegicus) Akibat Pemberian Asam Asetil Salisilat, Skripsi, Fakultas Kedokteran Hewan Institut Pertanian Bogor, Bogor.

Putri, P.A., 2012, Penurunan Efek Ulserogenik Piroksikam Melalui Pembentukan Dispersi Padat Piroksikam-PVP pada Tikus Putih Jantan, Skripsi, Fakultas Farmasi Universitas Ahmad Dahlan, Yogyakarta.

Reid, R., Robberts, F., and Macduff, E., 2011, Pathology Illustrated, seventh edition, 297-306, Churchill Livingstone, New York.

Sahumena, M.H., 2014, Pengembangan Nanopartikel Ketoprofen dengan Teknik Self-nanoemulsifying Drug Delivery System (SNEDDS) dan Uji Aktivitas Antiinflamasi, Tesis, Fakultas Farmasi Universitas Gajah Mada, Yogyakarta.

Smith, B.J., and Mangkoewidjojo, S., 1988, Pemeliharaan, Pembiakan dan Penggunaan Hewan Cobaan di Daerah Tropis, Universitas Indonesia Press, Jakarta.

Syafitri, A. S., 2014, Keamanan dan Khasiat Mutu Kemangi, Pustaka Baru Press, Yogyakarta.

Szabo, S., Trier, J.S,, Brown, A., Schnoor, J., Homan, H.D., and Bradford, J.C., 1985, A quantitative method for assessing the extent of experimental gastric erosions and ulcers, Journal of Pharmacological Methods, 13: 59-66.

Sung, J. J., Kuipers, E. J., and El-Serag, H. B., 2009, Systematic review: The Global Incidence and Prevalence of Peptic Ulcer Disease, Alimentary Pharmacology Therapeutic, 29 (90): 38-46.

Thakur, A., Walia, M.K., and Kumar S.L.H., 2013, Nanoemulsion In Enhancement of Bioavailability of Poorly Soluble Drug: A Review, Pharmacophore, 4(1): 15-25.

Thomson, R.G., 1984, General Veterinary Pathology, second edition, 112, Saunders Company, Philadelphia.

Tortora, G.J., and Derrickson, B.H., 2009, Principles of Anatomy and Physiology, Twelfth edition, 937-941, John Willey, USA.

Trivedi M.K., Patil S., Shettigar H., Bairwa, K., and Jana, S., 2015, Effect of Biofield Treatment on Spectral Properties of Paracetamol and Piroxicam, Chemical Sciences Journal, 6: 98.

Tsukimi, Y., and Okabe, S., 2001, Recent Advences in Gastrointestinal Phatophysiology: Role of Heat Shock Protein in Mucosal Defense and Ulcer Healing, Biol Pharm Bull, 24(1):1-9.

Underwood, J.C.E., 1999, Patologi Umum & Sistemik (General & Systemic Pathology), Volume I, Edisi II, 640-641, diterjemahkan oleh Sarjadi, Penerbit Buku Kedokteran EGC, Jakarta.

Wallace, J.L., 2001, Pathogenesis of NSAID-Induced Gastroduodenal Mucosal Injury, Gastroenterology, 15(5): 691-703.

Wallace, J.L., 2008, Prostaglandins, NSAID, and Gastric Mucosal Protection: Why Doesn’t the Stomach Digest Itself?, Physiological Revies, 88: 1547- 1565.

Wallace, J.L., and Vong, L., 2008, NSAID-induced Gastrointestinal Damage and The Design of GI-sparing NSAIDs, Current Opinion in Investigational Drugs, 9 (11): 151-1156.

Wang, L., Jinfeng Dong, J., Eastoe J., and Li, X., 2009, Design and optimization of a new self-nanoemulsifying drug delivery systems, Journal of Colloid and Interface Science, 330: 443-448.

Wilmana, P.F., dan Gan S., 2007, Analgesik Antipiretik Analgesik Anti Inflamasi Nonsteroid dan Obat Gangguan Sendi Lainnya dalam Farmakologi dan Terapi, Edisi V, 230-246, Balai Penerbit FKUI, Jakarta.

Wu, C.Y., and Benet, L.Z., 2005, Predicting Drug Dispotition Via Application of BCS: Transpot/ Absorption/ Elimination Interplay and Development of aBiopharmaceutics Drug Disposition Classification System, Pharmaceutical Research, 22(1): 11-23.

Yadav, V.K., Gupta, A.B., Kumar, R., Yadav, J.S., and Kumar, B., 2010, Mucoadhesive Polymers: Means of Improving the Mucoadhesive Properties of Drug Delivery System, Journal of Chemical and Pharmaceutical Research, 2(5): 418-432.

Yuliani, S.H., Hartini, M., Stephanie., Pudyastuti, B., Istyastono, E.P., 2016, Comparison of Physical Stability Properties of Pomegranate Seed Oil Nanoemulsion Dosage Forms with Long Chain Triglyceride and Medium- Chain Triglyceride As the Oil Phase, Traditional Medicine Journal, 21(2): 93-98.

Zhao, Y., Wang, C., Chow A.H., Ren, K., Gong, T., Zhang, Z. and Zheng, Y., 2010, Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of Zedoary essential oil: Formulation and bioavailability studies, International Journal of Pharmaceutics, 383: 170-177.




DOI: http://dx.doi.org/10.12928/pharmaciana.v8i2.11478

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