Advertisement
Research Article Pharmaceutics, Drug Delivery and Pharmaceutical Technology| Volume 110, ISSUE 3, P1270-1278, March 01, 2021

In situ Formed Implants, Based on PLGA and Eudragit Blends, for Novel Florfenicol Controlled Release Formulations

Published:November 17, 2020DOI:https://doi.org/10.1016/j.xphs.2020.11.006

      Abstract

      Drug controlled release technologies (DCRTs) represent an opportunity for designing new therapies. Main objectives are dose number optimization and secondary effects reduction to improve the level of patient/client acceptance. The present work studies DCRTs based in blended polymeric implants for single dose and long-term therapies of florfenicol (FF), a broad spectrum antibiotic. Polymers used were PLGA and Eudragit E100/S100 types. Eudragit/PLGA and FF/PLGA ratios were the main studied factors in terms of encapsulation efficiencies (EEs) and drug release profiles. In addition, morphological and physicochemical characterization were carried out. EEs were of 50–100% depending on formulation composition, and the FF releasing rate was increased or diminished when E100 or S100 were added, respectively. PLGA hydrolytic cleavage products possibly affect Eudragit solubility and matrix stability. Different mathematical models were used for better understanding and simulating release processes. Implants maintained the antimicrobial activity against Pseudomonas aeruginosa up to 12 days on agar plates. The developed DCRTs represents a suitable alternative for florfenicol long-term therapies.

      Keywords

      To read this article in full you will need to make a payment
      APhA Member Login
      APhA Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Rodrigues de Azevedo C.
        • von Stosch M.
        • Costa M.S.
        • et al.
        Modeling of the burst release from PLGA micro- and nanoparticles as function of physicochemical parameters and formulation characteristics.
        Int J Pharm. 2017; 532: 229-240
        • Fu Y.
        • Kao W.J.
        Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems.
        Expet Opin Drug Deliv. 2010; 7: 429-444
        • Winzenburg G.
        • Schmidt C.
        • Fuchs S.
        • Kissel T.
        Biodegradable polymers and their potential use in parenteral veterinary drug delivery systems.
        Adv Drug Deliv Rev. 2004; 56: 1453-1466
        • Hans M.
        • Lowman A.
        Biodegradable nanoparticles for drug delivery and targeting.
        Curr Opin Solid State Mater Sci. 2002; 6: 319-327
        • Patel H.
        • Panchal D.R.
        • Patel U.
        • Brahmbhatt T.
        • Suthar M.
        Matrix type drug delivery System: a review.
        JPSBR. 2011; 1: 143-151
        • Thakur R.R.S.
        • McMillan H.L.
        • Jones D.S.
        Solvent induced phase inversion-based in situ forming controlled release drug delivery implants.
        J Control Release. 2014; 176: 8-23
        • Parent M.
        • Nouvel C.
        • Koerber M.
        • Sapin A.
        • Maincent P.
        • Boudier A.
        PLGA in situ implants formed by phase inversion: critical physicochemical parameters to modulate drug release.
        J Control Release. 2013; 172: 292-304
        • Patel A.
        • Ansari T.
        • Vimal P.
        • Goyani M.
        • Deshmukh A.
        • Akbari B.
        Review on PLGA based solvent induced in- situ forming implant.
        Inven Spreading Knowl. 2015; 2015: 1-14
        • Sun Y.
        • Jensen H.
        • Petersen N.J.
        • Larsen S.W.
        • Østergaard J.
        Concomitant monitoring of implant formation and drug release of in situ forming poly (lactide-co-glycolide acid) implants in a hydrogel matrix mimicking the subcutis using UV–vis imaging.
        J Pharm Biomed Anal. 2018; 150: 95-106
        • Astaneh R.
        • Erfan M.
        • Moghimi H.
        • Mobedi H.
        Changes in morphology of in situ forming PLGA implant prepared by different polymer molecular weight and its effect on release behavior.
        J Pharm Sci. 2009; 98: 135-145
        • Eliaz R.E.
        • Kost J.
        Characterization of a Polymeric PLGA-Injectable Implant Delivery System for the Controlled Release of Proteins.
        J Biomed Mater Res., 1999
        • Anderson J.M.
        • Shive M.S.
        Biodegradation and biocompatibility of PLA and PLGA microspheres.
        Adv Drug Deliv Rev. 2012; 64: 72-82
        • Makadia H.K.
        • Siegel S.J.
        Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier.
        Polymers. 2011; 3: 1377-1397
        • Park T.G.
        Degradation of poly(lactic-co-glycolic acid) microspheres: effect of copolymer composition.
        Biomaterials. 1995; 16: 1123-1130
        • Busatto C.
        • Pesoa J.
        • Helbling I.
        • Luna J.
        • Estenoz D.
        Heterogeneous hydrolytic degradation of poly(lactic- co -glycolic acid) microspheres: mathematical modeling.
        J Appl Polym Sci. 2017; 134: 45464
        • Ramchandani M.
        • Robinson D.
        In vitro and in vivo release of ciprofloxacin from PLGA 50: 50 implants.
        . 1998; 54: 167-175
        • Koocheki S.
        • Madaeni S.S.
        • Niroomandi P.
        Development of an enhanced formulation for delivering sustained release of buprenorphine hydrochloride.
        Saudi Pharm J. 2011; 19: 255-262
        • Patra C.N.
        • Priya R.
        • Swain S.
        • Kumar Jena G.
        • Panigrahi K.C.
        • Ghose D.
        Pharmaceutical significance of Eudragit®: a review.
        Futur J Pharm Sci. 2017; 3: 33-45
        • Sonje A.
        • Chandra A.
        Comprehensive review on Eudragit® polymers.
        Int Res J Pharm. 2013; 4: 71-74
        • Sonia P.
        • Mattha S.
        • Mansha U.
        • Arti G.
        • Hetal P.
        • Jitendra Y.
        Cell line and augument cellular uptake study of statistically optimized sustained release capecitabine loaded Eudragit S100/PLGA(poly(lactic- co-glycolic acid)) nanoparticles for colon targeting.
        Curr Drug Deliv. 2017; 14: 887-899
        • Cetin M.
        • Atila A.
        • Kadioglu Y.
        Formulation and in vitro characterization of Eudragit ® L100 and Eudragit ® L100-PLGA nanoparticles containing diclofenac sodium formulation and in vitro characterization of Eudragit ® L100 and Eudragit ® L100-PLGA nanoparticles containing diclofenac sodi.
        AAPS PharmSciTech. 2010; 11: 1250-1256
        • Smith A.W.
        Biofilms and antibiotic therapy: is there a role for combating bacterial resistance by the use of novel drug delivery systems?.
        Adv Drug Deliv Rev. 2005; 57: 1539-1550
        • Feczkó T.
        • Tóth J.
        • Dósa G.
        • Gyenis J.
        Optimization of protein encapsulation in PLGA nanoparticles.
        Chem Eng Process Process Intensif. 2011; 50: 757-765
        • Sidhu P.
        • Rassouli A.
        • Illambas J.
        • et al.
        Pharmacokinetic-pharmacodynamic integration and modelling of florfenicol in calves.
        J Vet Pharmacol Ther. 2014; 37: 231-242
        • Wang S.
        • Chen N.
        • Qu Y.
        Solubility of florfenicol in different solvents at temperatures from (278 to 318) K.
        J Chem Eng Data. 2011; 56: 638-641
        • Song M.
        • Li Y.
        • Ning A.
        • Fang S.
        • Cui B.
        Silica nanoparticles as a carrier in the controlled release of florfenicol.
        J Drug Deliv Sci Technol. 2010; 20: 349-352
        • Kou X.
        • Li Q.
        • Lei J.
        • et al.
        Preparation of molecularly imprinted nanospheres by premix membrane emulsification technique.
        J Memb Sci. 2012; 417–418: 87-95
        • Rogel C.
        • Mendoza N.
        • Troncoso J.
        • González J.
        • Von Plessing C.
        Formulation and characterization of inclusion complexes using hydroxypropyl-β-cyclodextrin and florfenicol with chitosan microparticles.
        J Chil Chem Soc. 2011; 56: 574-579
        • Ling Z.
        • Yonghong L.
        • Changqing S.
        • et al.
        Preparation, characterization, and pharmacokinetics of tilmicosin- and florfenicol-loaded hydrogenated castor oil-solid lipid nanoparticles.
        J Vet Pharmacol Ther. 2017; 40: 293-303
        • Karp F.
        • Busatto C.
        • Turino L.
        • Luna J.
        • Estenoz D.
        PLGA nano- and microparticles for the controlled release of florfenicol: experimental and theoretical study.
        J Appl Polym Sci. 2019; 136: 47248
        • Helbling I.M.
        • Ibarra J.C.D.
        • Luna J.A.
        The use of cellulose membrane to eliminate burst release from intravaginal rings.
        AAPS J. 2016; 18: 960-971
        • Islan G.A.
        • Ruiz M.E.
        • Morales J.F.
        • et al.
        Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: physicochemical characterization and in vivo targeted delivery to the lungs.
        J Mater Chem B. 2017; 5: 3132-3144
        • Turner K.H.
        • Everett J.
        • Trivedi U.
        • Rumbaugh K.P.
        • Whiteley M.
        Requirements for Pseudomonas aeruginosa Acute burn and chronic surgical wound infection.
        PLoS Genet. 2014; 10: e1004518
        • Cross A.
        • Allen J.R.
        • Burke J.
        • et al.
        Nosocomial infections due to Pseudomonas aeruginosa: review of recent trends.
        Clin Infect Dis. 1983; 5: S837-S845
        • Zhang Q.
        • Tang S.S.
        • Qian M.Y.
        • et al.
        Nanoemulsion formulation of florfenicol improves bioavailability in pigs.
        J Vet Pharmacol Ther. 2016; 39: 84-89
        • Solorio L.
        • Olear A.M.
        • Hamilton J.I.
        • et al.
        Noninvasive characterization of the effect of varying PLGA molecular weight blends on in situ forming implant behavior using ultrasound imaging.
        Theranostics. 2012; 2: 1064-1077
        • Karp F.
        • Turino L.N.
        • Estenoz D.
        • Castro G.R.
        • Islan G.A.
        Encapsulation of florfenicol by in situ crystallization into novel alginate- Eudragit RS ® blended matrix for pH modulated release.
        J Drug Deliv Sci Technol. 2019; 54: 101241
        • Sackett C.K.
        • Narasimhan B.
        Mathematical modeling of polymer erosion: consequences for drug delivery.
        Int J Pharm. 2011; 418: 104-114
      1. Mathematical models of drug release.
        in: Strategies to Modify the Drug Release from Pharmaceutical Systems. Elsevier, Amsterdam, Netherlands2015: 63-86
        • Romero V.L.
        • Pons P.
        • Bocco J.L.
        • Manzo R.H.
        • Alovero F.L.
        Eudragit® E100 potentiates the bactericidal action of ofloxacin against fluoroquinolone-resistant Pseudomonas aeruginosa.
        FEMS Microbiol Lett. 2012; 334: 102-110
        • Pawar P.
        • Sharma P.
        • Chawla A.
        • Mehta R.
        Formulation and in vitro evaluation of Eudragit® S-100 coated naproxen matrix tablets for colon-targeted drug delivery system.
        J Adv Pharm Technol Res. 2013; 4: 31
        • Sun Z.
        • Hao H.
        • Xie C.
        • et al.
        Thermodynamic properties of form A and form B of florfenicol.
        Ind Eng Chem Res. 2014; 53: 13506-13512
        • Valizadeh H.
        • Nokhodchi A.
        • Qarakhani N.
        • et al.
        Physicochemical characterization of solid dispersions of indomethacin with PEG 6000, myrj 52, Lactose, sorbitol, dextrin, and Eudragit® E100.
        Drug Dev Ind Pharm. 2004; 30: 303-317
        • Goddeeris C.
        • Willems T.
        • Houthoofd K.
        • Martens J.A.
        • Van den Mooter G.
        Dissolution enhancement of the anti-HIV drug UC 781 by formulation in a ternary solid dispersion with TPGS 1000 and Eudragit E100.
        Eur J Pharm Biopharm. 2008; 70: 861-868
        • Thakral N.K.
        • Ray A.R.
        • Majumdar D.K.
        Eudragit S-100 Entrapped Chitosan Microspheres of Valdecoxib for Colon Cancer.
        J Mater Sci Mater Med., 2010: 2691-2699
        • Marciniec B.
        • Stawny M.
        • Hofman M.
        • Naskrent M.
        Thermal and spectroscopic analysis of florfenicol irradiated in the solid-state.
        J Therm Anal Calorim. 2008; 93: 733-737
        • Prudic A.
        • Lesniak A.K.
        • Ji Y.
        • Sadowski G.
        Thermodynamic phase behaviour of indomethacin/PLGA formulations.
        Eur J Pharm Biopharm. 2015; 93: 88-94
        • Smith R.P.
        Aeruginosa quorum-sensing systems and virulence.
        Curr Opin Microbiol. 2003; 6: 56-60