Anti-Inflammatory and Gastroprotective Properties of Aspirin - Entrapped Solid Lipid Microparticles

Author(s): Salome A. Chime*, Paul A. Akpa, Cosmas C. Ugwuanyi, Anthony A. Attama

Journal Name: Recent Patents on Inflammation & Allergy Drug Discovery (Discontinued)

Volume 14 , Issue 1 , 2020

Abstract:

Background: Aspirin is a nonsteroidal anti-inflammatory drug that is very effective in the treatment of inflammation and other health conditions, however, it causes gastric irritation. Recently, researchers have developed patents (US9757529, 2019) of inhalable aspirin for rapid absorption and circumvention of gastric irritation.

Objective: The aim of this work was to formulate aspirin-loaded lipid based formulation in order to enhance oral bioavailability and inhibit gastric irritation.

Methods: This solid lipid microparticles loaded with aspirin (SLM) was formulated by a modified cold homogenization-solvent evaporation method. In vitro studies such as in vitro drug release, particle size, Encapsulation Efficiency (EE), micromeritic properties and loading capacity were carried out. Pharmacodynamics studies such as anti-inflammatory and ulcerative properties of the SLM were also carried out in Wistar rats.

Results: The results showed that aspirin entrapped SLM exhibited the highest EE of 72% and particle size range of 7.60 + 0.141µm to 20.25 + 0.070µm. Formulations had about 55% drug release at 6h in simulated intestinal fluid pH 6.8. The formulations had good flowability that could facilitate filling into hard gelatin capsule shells. The SLM exhibited 100% gastroprotection against aspirin-induced ulcers (p < 0.05). The percentage of anti-inflammatory activities also showed that aspirin-entrapped SLM had 78% oedema inhibition at 7h, while the reference had 68% inhibition at 7h.

Conclusion: Aspirin-entrapped SLM showed good sustained-release properties, enhanced antiinflammatory properties and total gastric protection from aspirin-induced ulcers and could be used as once-daily oral aspirin.

Keywords: Anti-inflammatory, aspirin, drug delivery, gastroprotection, kinetics of release, lipids, micromerics, ulcers.gugu

[1]
Charles RC, Bruce RK, Laura KS. Formulation of acetylsalicylic acid tablets for aqueous enteric film coating. Pharm Tech Drug Del 2001; 13(5): 44-53.
[2]
Gugu TH, Chime SA, Attama AA. Solid lipid microparticles: An approach for improving oral bioavailability of aspirin. Asian J Pharm Sci 2015; 10(5): 425-32.
[http://dx.doi.org/10.1016/j.ajps.2015.06.004]
[3]
Mitrevej A, Hollenbeck RG. Influence of hydrophilic excipients on the interaction of aspirin and water. Int J Pharm 1983; 14: 243-50.
[http://dx.doi.org/10.1016/0378-5173(83)90097-2]
[4]
Ugurlucan M, Caglar IM, Caglar FN, Ziyade S, Karatepe O, Yildiz Y, et al. Aspirin: from a historical perspective. Recent Pat Cardiovasc Drug Discov 2012; 7(1): 71-6.
[http://dx.doi.org/10.2174/157489012799362377] [PMID: 22257089]
[5]
Mirshafiey A, Mortazavi-Jahromi SS, Taeb M, Cuzzocrea S, Esposito E. Evaluation of the Effect of α-L-guluronic acid (G2013) on COX-1, COX-2 activity and gene expression for introducing this drug as a novel NSAID with immunomodulatory property. Recent Pat Inflamm Allergy Drug Discov 2018; 12(2): 162-8.
[http://dx.doi.org/10.2174/1872213X12666180607121809] [PMID: 29879894]
[6]
Capodanno D, Angiolillo DJ. Aspirin for primary cardiovascular risk prevention and beyond in diabetes mellitus. Circulation 2016; 134(20): 1579-94.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.023164] [PMID: 27729421]
[7]
Lewin G. Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2007; 146(5): 361-4.
[http://dx.doi.org/10.7326/0003-4819-146-5-200703060-00008] [PMID: 17339621]
[8]
Cao Y, Nishihara R, Qian ZR. Song M, Mima K, Inamura K, et al.Regular aspirin use associates with lower risk of colorectal cancers with low numbers of tumor-infiltrating lymphocytes. Gastroenterology 2016; 151(5): 879-892.e4.
[http://dx.doi.org/10.1053/j.gastro.2016.07.030] [PMID: 27475305]
[9]
Cuzick J, Otto F, Baron JA. Brown PH, Burn J, Greenwald P, et al.Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol 2009; 10: 501-7.
[http://dx.doi.org/10.1016/S1470-2045(09)70035-X]
[10]
Singh Ranger G. The role of aspirin in colorectal cancer chemoprevention. Crit Rev Oncol Hematol 2016; 104: 87-90.
[http://dx.doi.org/10.1016/j.critrevonc.2016.05.011] [PMID: 27289249]
[11]
Cappelaere P, Adenis L, Driessens J. [Value of injectable aspirin in cancerology]. Lille Med 1971; 17: 3-, 566-571.
[PMID: 5153016]
[12]
Kambiz Y. Dry powder inhaler and methods of use. US9757529 (2019).
[13]
Kambiz Y. Dry powder aspirin compositions with magnesium stearate. US10195147 (2019).
[14]
Kumud KP, Nilamkumari SP, Sunil CK, Amit M, Indravadan AM, Rajiv IM. Stable pharmaceutical composition for atherosclerosis. CN102480954 (2015).
[15]
Somberg JC, Ranade VV. Formulation of aspirin that is stable and showing minimal hydrolysis for parenteral adminstration for the treatment of cardiovascular and other disease states.US20100173875 (2010).
[16]
Manoj S, James B, Robert S. Enteric coated aspirin granules comingled with binder. US8057820 (2011)
[17]
Bilgiç M. Pharmaceutical formulations containing atorvastatin and aspirin. TR201005325 (2010).
[18]
Humera A, Jing L, Ram G. Aspirin soft gelatin capsule as a single active or in combination with other actives. WO2017095736 (2017).
[19]
Jaiswal S, Krishna S, Shirish K. Compact solid dosage form of aspirin and clopidogrel. WO2017037741 (2017).
[20]
Brenne JF, Frédérique C, Georges D, Edeline-berlemont J, Fontaine N. Pharmaceutical tablet comprising acetylsalicylic acid and clopidogrel. WO2015014766 (2015).
[21]
Fumitoshi A, Atsuhiro S, Taketoshi O, Teruhiko I. Method of treatment with coadministration of aspirin and prasugrel.US8569325 (2013).
[22]
Kelly JP. Use of caffeine and aspirin in synergistic amounts for improving performance. WO2011117322 (2012).
[23]
Jacob JN. Formulations from natural products, turmeric, and aspirin.CA2786255 (2011).
[24]
Thakkar A, Sutaria D, Grandhi BK, Wang J, Prabhu S. The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer. Oncol Rep 2013; 29(4): 1671-7.
[http://dx.doi.org/10.3892/or.2013.2276] [PMID: 23404329]
[25]
Zhou L, Duan X, Zeng S, et al. Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis. Int J Nanomedicine 2015; 10(1): 5205-18.
[http://dx.doi.org/10.2147/IJN.S84326] [PMID: 26316750]
[26]
Hossain MA, Kim DH, Jang JY, et al. Aspirin enhances doxorubicin-induced apoptosis and reduces tumor growth in human hepatocellular carcinoma cells in vitro and in vivo. Int J Oncol 2012; 40(5): 1636-42.
[PMID: 22322725]
[27]
Dihlmann S, Siermann A, von Knebel Doeberitz M. The nonsteroidal anti-inflammatory drugs aspirin and indomethacin attenuate beta-catenin/TCF-4 signaling. Oncogene 2001; 20(5): 645-53.
[http://dx.doi.org/10.1038/sj.onc.1204123] [PMID: 11313997]
[28]
Dihlmann S, Klein S, Doeberitz Mv Mv. Reduction of beta-catenin/T-cell transcription factor signaling by aspirin and indomethacin is caused by an increased stabilization of phosphorylated beta-catenin. Mol Cancer Ther 2003; 2(6): 509-16.
[PMID: 12813129]
[29]
Hammerlindl H, Ravindran Menon D, Hammerlindl S, et al. Acetylsalicylic acid governs the effect of sorafenib in RAS‐mutant cancers. Clin Cancer Res 2018; 24(5): 1090-102.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2118] [PMID: 29196297]
[30]
Hu LX, Du YY, Zhang Y, Pan YY. Synergistic effects of exemestane and aspirin on MCF-7 human breast cancer cells. Asian Pac J Cancer Prev 2012; 13(11): 5903-8.
[http://dx.doi.org/10.7314/APJCP.2012.13.11.5903] [PMID: 23317278]
[31]
Shanta D, Rakesh P. Prodrug for release of cisplatin and cyclooxygenase inhibitor. WO2015089389 (2015).
[32]
Brown SA, Chime SA, Attama AA, Agu C, Onunkwo GC. In vitro and in vivo characterisation of piroxicam-loaded DIKA wax lipospheres. Trop J Pharm Res 2013; 12(1): 33-8.
[http://dx.doi.org/10.4314/tjpr.v12i1.6]
[33]
Eradel MS, Gungor S, Ozsoy Y, Araman A. Preparation and in vitro evaluation of indomethacin loaded solid lipid microparticles. Acta Pharmaceiutical Sciencia 2009; 51: 203-10.
[34]
Obitte NC, Ofokansi KC, Chime SA, Odimegwu DC, Ezema AO, Odoh UE. A preliminary attempt to address indomethacin’s poor water solubility using solid self-emulsifying drug delivery system as a carrier. Afr J Pharm Pharmacol 2013; 7(46): 2918-27.
[http://dx.doi.org/10.5897/AJPP2012.1510]
[35]
Obitte NC, Chime SA, Magaret AA, Attama AA, Onyishi IV, Brown SA. Some in vitro and pharmacodynamic evaluation of indomethacin solid lipid microparticles. Afr J Pharm Pharmacol 2012; 6(30): 2309-17.
[http://dx.doi.org/10.5897/AJPP12.524]
[36]
Nanjwade BK, Patel DJ, Udhani RA, Manvi FV. Functions of lipids for enhancement of oral bioavailability of poorly water-soluble drugs. Sci Pharm 2011; 79(4): 705-27.
[http://dx.doi.org/10.3797/scipharm.1105-09] [PMID: 22145101]
[37]
Long C, Zhang L, Qian Y. Preparation and crystal modification of Ibuprofen-loaded solid lipid microparticles. Chin J Chem Eng 2006; 14(4): 518-25.
[http://dx.doi.org/10.1016/S1004-9541(06)60107-9]
[38]
Attama AA, Müller-Goymann CC. A critical study of novel physically structured lipid matrices composed of a homolipid from Capra hircus and theobroma oil. Int J Pharm 2006; 322(1-2): 67-78.
[http://dx.doi.org/10.1016/j.ijpharm.2006.05.044] [PMID: 16828247]
[39]
Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. Eur J Pharm Sci 2000; 11(Suppl. 2): S93-8.
[http://dx.doi.org/10.1016/S0928-0987(00)00167-6] [PMID: 11033431]
[40]
Fricker G, Kromp T, Wendel A, et al. Phospholipids and lipid-based formulations in oral drug delivery. Pharm Res 2010; 27(8): 1469-86.
[http://dx.doi.org/10.1007/s11095-010-0130-x] [PMID: 20411409]
[41]
Richard J, Fais F, Baldascini H. Solid lipid microcapsules containing hGH. WO2010017965 (2010).
[42]
Kaur IP, Verma MK. Process for preparing solid lipid sustained release nanoparticles for delivery of vitamins. US9907758 (2018).
[43]
Kaur IP, Bhandari R. Solid lipid nanoparticles entrapping hydrophilic/amphiphilic drug and process for preparing the same.WO2013105101 (2014).
[44]
Zhou Y, Wang N, Wang T. Novel preparation method of solid lipid nanoparticles. CN201010112202 (2010).
[45]
Sobrinho Soares JL, Melo Tiburcio CDCS, De Freitas FHRDRMDLS, Oliveira De Lacerda NPCD. Production of lipid nanoparticles by microwave synthesis. WO2018109690 (2018).
[46]
Burke P, Gindy M, Mathre D. Preparation of lipid nanoparticles.WO2011127255 (2011).
[47]
Repka MA, Patil HG, Majumdar S, Park JB, Kulkarni VI. Systems and methods for preparing solid lipid nanoparticles.WO2015148483 (2015).
[48]
Weiss J, Schweiggert C, Leuenberger B, Novotny M, Tedeschi C, Kessler A. Solid lipid nanoparticles (I). US9616001 (2017).
[49]
Sun JH, Yuan H, Liu F, Chen SQ. Solid lipid magnetic resonance nanoparticles and preparation method and use thereof.WO2017041609 (2017).
[50]
Munhoz A, De Vecchi R, Eduardo Durán Caballero N, Xavier Pinto Dini A, De Jesus MB. Nanostructured lipid carriers and methods for making and using them. WO2017185155 (2017).
[51]
Mosqueira CF, Oliveira LT, Castanheira RG. Micro- and nanostructured pharmaceutical and veterinary compositions, containing benznidazole and derivatives thereof, which form micro and nanostructures in the gastrointestinal tract, and biologicals uses thereof. WO2015039199 (2015).
[52]
Bara I. Composition of Pickering emulsion type based on hydrophobic silica particles. WO2013076673 (2013).
[53]
Lauriane A, Studart A, Tervoort E, Leuenberger B, Teleki A, Mesaros S. Pickering emulsions. WO2016124522 (2016).
[54]
Karasulu HY, Apaydin S, Gundogdu E, et al. Selfmicro/nanoemulsifying drug carrying system for oral use of rosuvastatin.WO2015142307 (2015).
[55]
Premchand N, Prashant M, Girish KG, Munish T. Selfemulsifying pharmaceutical compositions of rhein or diacerein.US8999381 (2015).
[56]
Shabaik Y, Jiao J, Pujara CP. Self-Emulsifying Drug Delivery System (SEDDS) for ophthalmic drug delivery. WO2016141098 (2016).
[57]
Khan MA, Nazzal S. Eutectic-based self-nanoemulsified drug delivery system. US8790723 (2014).
[58]
Bansal AK, Munjal B, Patel SB. Self-nano-emulsifying curcuminoids composition with enhanced bioavailability. WO2010010431 (2010).,
[59]
Garti N, Aserin A, Libster D, Mishraki T, Amar-Yuli I, Bitan-Chervkovsky L. Reverse hexagonal mesophases (hii) and uses thereof. WO2010150262 (2011).
[60]
Dahl-Kyun OH, Kyun-Young L. Preparation of nanoliposomeencapsulating proteins and protein-encapsulated nanoliposome.US7951396 (2011).
[61]
Fatmi A, Kim TKE. Methods for enhancing the release and absorption of water insoluble active agents. WO2010075065 (2010).
[62]
Wu N, Keller BC. Lipid drug conjugates for drug delivery. WO2010107487 (2010).
[63]
Pratibha SP, Maharukh TR, Anilkumar SG. Sustained release compositions of anti-alzheimer's agents. WO2012035409 (2012).
[64]
Yerramilli VSN. Phospholipid gel compositions for drug delivery and methods of treating conditions using same. US7846472 (2010).
[65]
Satyavani K, Ramanathan T, Gurudeeban S, Balasubramanian T. Drug for treatment of diabetes and diabetic foot ulcer using rutin loaded solid lipid nanoparticles. IN718/CHE/2013 (2013).
[66]
Kumar SS, Mohanty C. A novel water soluble curcumin loaded nanoparticulate system for cancer therapy. WO2011101859 (2011).,
[67]
Sally AF, Gregory MC. Bioavailable curcuminoid formulations for treating Alzheimer's disease and other age-related disorders.US20090324703 (2009).
[68]
Vassal GP, Ioulalen K, Brun BC, Lassu N. Galenic form under the form of solid lipid particles, useful in pediatrics, comprise temozolomide in lipid matrix, where the matrix comprises triglycerides with saturated fatty acids, and a mixture of fatty acids with specific fatty acids. FR2935270 (2010).
[69]
Luigi B, Elena U. Lipid Nano- and microparticles: An overview of patent-related research. J Nanomat 2019; 2019: Article ID 2834941.
[http://dx.doi.org/10.1155/2019/2834941]
[70]
Umeyor CE, Kenechukwu FC, Uronnachi EM, Osonwa UE, Nwakile CD. Solid Lipid Microparticles (SLMs): An effective lipid based technology for controlled drug delivery. Am J Pharm Tech Res 2012; 2(6): 1-18.
[71]
Viladot Petit JL. Lipid nanoparticles capsules. WO2011116963 (2011).
[72]
Benoit JP, Ferrier T. Method for preparing functionalized lipid capsules. WO2010113111 (2010).
[73]
Galuska PE, Rasmussen LM. Processes for producing lipid particles.US2010233344 (2010).
[74]
Sanna V, Kirschvink N, Gustin P, et al. Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration. AAPS PharmSciTech 2004; 5(2) e27
[http://dx.doi.org/10.1208/pt050227] [PMID: 15760085]
[75]
Jaspart S, Bertholet P, Piel G, Dogné JM, Delattre L, Evrard B. Solid lipid microparticles as a sustained release system for pulmonary drug delivery. Eur J Pharm Biopharm 2007; 65(1): 47-56.
[http://dx.doi.org/10.1016/j.ejpb.2006.07.006] [PMID: 16962749]
[76]
Jaspart S, Piel G, Delattre L, Evrard B. Solid lipid microparticles: formulation, preparation, characterisation, drug release and applications. Expert Opin Drug Deliv 2005; 2(1): 75-87.
[http://dx.doi.org/10.1517/17425247.2.1.75] [PMID: 16296736]
[77]
Chime SA, Attama AA, Onunkwo GC. Application of SRMS 154 as sustained release matrix for the delivery of stavudine: In vitro and in vivo evaluation and effect of Poloxamer 188 on the properties of the tablets. Infect Disord Drug Targ 2019.
[http://dx.doi.org/10.2174/1871526519666190313162635.]
[78]
Onyishi VI, Chime SA, Adibe CV. Formulation of pyridoxine hydrochloride sustained release capsules: Effect of propylene glycol co-solvent on the in vitro release. Afr J Pharm Pharmacol 2013; 7(15): 809-15.
[http://dx.doi.org/10.5897/AJPP2013.3528]
[79]
Onyishi IV, Chime SA, Okoroji CA. Physicochemical properties of microcrystalline cellulose from Saccharum officinarum: Comparative evaluation with Avicel® pH 101. Am J Pharm Tech Res 2013; 3(5): 414-26.
[80]
Aulton ME. Pharmaceutics; The Science of Dosage Form Design. 1st ed. Edinburgh: Churchill Living Stone 1999.
[81]
Aulton ME. Pharmaceutics; The Science of Dosage Form Design. 3rd ed. Edinburgh: Churchill Living Stone 2007; pp. 197-210.
[82]
Chinaeke EE, Chime SA, Onyishi IV, Attama AA, Okore VC. Formulation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids. Drug Deliv 2014; 20(5): 546-54.
[PMID: 24479677]
[83]
Chinaeke EE, Chime SA, Kenechukwu FC, Müller-Goymann CC, Attama AA, Okore VC. Formulation of novel artesunate-loaded Solid Lipid Microparticles (SLMs) based on DIKA wax matrices: In vitro and in vivo evaluation. J Drug Deliv Sci Technol 2014; 24(1): 69-77.
[http://dx.doi.org/10.1016/S1773-2247(14)50010-X]
[84]
Attama AA, Okafor CE, Builders PF, Okorie O. Formulation and in vitro evaluation of a PEGylated microscopic lipospheres delivery system for ceftriaxone sodium. Drug Deliv 2009; 16(8): 448-57.
[http://dx.doi.org/10.3109/10717540903334959] [PMID: 19839789]
[85]
Umeyor EC, Kenechukwu FC, Ogbonna JD, Chime SA, Attama A. Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo. J Microencapsul 2012; 29(3): 296-307.
[http://dx.doi.org/10.3109/02652048.2011.651495] [PMID: 22283701]
[86]
Chime SA, Attama AA, Builders PF, Onunkwo GC. Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation. J Microencapsul 2013; 30(4): 335-45.
[http://dx.doi.org/10.3109/02652048.2012.726284] [PMID: 23057661]
[87]
Kenechukwu FC, Attama AA, Ibezim EC, Nnamani PO. Umeyor CE, Uronnachi EM, et al.Novel intravaginal drug delivery system based on molecularly pegylated lipid matrices for improved antifungal activity of miconazole nitrate. BioMed Res Int 2019; 2018 3714329.
[88]
Uronnachi EM, Ogbonna JDN, Kenechukwu FC, Attama AA, Chime SA. Properties of zidovudine loaded solidified reverse micellar microparticles prepared by melt dispersion. J Pharm Res 2012; 5(5): 2870-4.
[89]
Chinaeke EE, Chime SA, Ogbonna JDN, Attama AA, Müller-Goymann CC, Okore VC. Evaluation of dika wax-soybean oil-based artesunate-loaded lipospheres: in vitro-in vivo correlation studies. J Microencapsul 2014; 31(8): 796-804.
[http://dx.doi.org/10.3109/02652048.2014.940008] [PMID: 25090593]
[90]
Kenechukwu FC, Umeyor CE, Momoh MA, Ogbonna JDN, Chime SA, Nnamani PO, et al. Evaluation of gentamicin-entrapped solid lipid microparticles formulated with a biodegradable homolipid from Capra hircus. Trop J Pharm Res 2014; 13(8): 1999-205.
[http://dx.doi.org/10.4314/tjpr.v13i8.2]
[91]
Kalam MA, Humayun M, Parvez N, Yadav S, Garg A, Amin S, et al. Release kinetics of modified pharmaceutical dosage forms: A review. Continental J Pharm Sci 2007; 1: 30-5.
[92]
Chime SA, Onunkwo GC, Onyishi IV. Kinetics and mechanisms of drug release from swellable and non swellable matrices: A review. Res J Pharm Biol Chem Sci 2013; 4(2): 97-103.
[93]
Higuchi T. Mechanism of sustained-action medication: Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci 1963; 52: 1145-9.
[http://dx.doi.org/10.1002/jps.2600521210] [PMID: 14088963]
[94]
Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci 1961; 50: 874-5.
[http://dx.doi.org/10.1002/jps.2600501018] [PMID: 13907269]
[95]
Ritger PL, Peppas NA. A simple equation for description of solute release 1. Fickian and non- Fickian release from non swellable device in the form of slabs, spheres, cylinders and discs. J Control Release 1987; 5: 23-36.
[http://dx.doi.org/10.1016/0168-3659(87)90034-4]
[96]
Pérez G RM. Anti-inflammatory activity of Ambrosia artemisiaefolia and Rhoeo spathacea. Phytomedicine 1996; 3(2): 163-7.
[http://dx.doi.org/10.1016/S0944-7113(96)80030-4] [PMID: 23194964]
[97]
Anosike AC, Onyechi O, Ezeanyika LUS, Nwuba MM. Anti-inflammatory and anti-ulcerogenic activity of the ethanol extract of ginger (Zingiber officinale). Afr J Biochem Res 2009; 3(12): 379-84.
[98]
Chung MC, dos Santos JL, Oliveira EV, Blau L, Menegon RF, Peccinini RG. Synthesis, ex vivo and in vitro hydrolysis study of an indoline derivative designed as an anti-inflammatory with reduced gastric ulceration properties. Molecules 2009; 14(9): 3187-97.
[http://dx.doi.org/10.3390/molecules14093187] [PMID: 19783917]
[99]
Momoh MA, Akpa PA, Attama AA. Phospholipon 90G based SLMs loaded with ibuprofen: An oral anti-inflammatory and gastrointestinal sparing evaluation in rats. Pak J Zool 2013; 44(6): 1657-64.
[100]
Chime SA, Onyishi VI. Lipid-based Drug Delivery Systems (LDDS): Recent advances and applications of lipids in drug delivery. Afr J Pharm Pharmacol 2013; 7(48): 3034-59.
[http://dx.doi.org/10.5897/AJPPX2013.0004]


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Article Details

VOLUME: 14
ISSUE: 1
Year: 2020
Published on: 30 March, 2020
Page: [78 - 88]
Pages: 11
DOI: 10.2174/1872213X14666200108101548

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