Araştırma Makalesi
BibTex RIS Kaynak Göster

Preparation and in vitro characterization of AL-Beads containing carbamazepine and/or levetiracetam

Yıl 2019, Cilt: 23 Sayı: 4, 642 - 651, 27.06.2025

Afife Büşra Uğur Kaplan , Büşra Kandilli Meltem Çetin , Fatma Demirkaya Miloğlu

Öz

The purpose of the present study was to prepare only levetiracetam (LEV) or carbamazepine (CBZ) or their combination (LEV+CBZ)-loaded alginate (AL) beads for oral administration to treat epilepsy and to evaluate their in vitro characteristics. AL beads were prepared using ionotropic gelation method and lyophilized. The bead formulations were evaluated for particles size, surface morphology, encapsulation efficiency and in vitro drug release in PB pH 6.8 and HCl pH 1.2 release mediums. FT-IR was also used to characterize the beads. The mean particle sizes of wet and lyophilized AL beads were in range of 1.609±0.073-1.779±0.078 mm and 1.075±0.182-1.275±0.138 mm, respectively. The encapsulation efficiency (EE%) values of bead formulations were in the range of 18.74-24.65% for LEV and 90.36-94.03% for CBZ. The pH of the medium affects the swelling behaviours of AL beads and the degree of swelling of AL beads increased with increase of pH of release medium, due to exchange of the Ca2+ ion with Na+. Besides, the pH of the release medium and the high water solubility of LEV affected the drug release rate from beads. AL beads might be useful to use for oral administration of LEV and CBZ to obtain additive/synergistic effect in a combined treatment of epilepsy.

Anahtar Kelimeler

Alginate beads carbamazepine; epilepsy in vitro characteristics levetiracetam.

Kaynakça

  • [1] Kumar P, Jhanjee A, Bhatia MS. Lacosamide: A new antiepileptic drug. Delhi Psychiatry J. 2010; 13(2): 356–366.
  • [2] Devinsky O, Vezzani A, O’Brien TJ, et al. Epilepsy. Nat Rev Dis Primers. 2018; 3: 18024. [CrossRef]
  • [3] Florek-Luszczki M, Wlaz A, Luszczki JJ. Interactions of levetiracetam with carbamazepine, phenytoin, topiramate and vigabatrin in the mouse 6Hz psychomotor seizure model – A type II isobolographic analysis. Eur J Pharmacol. 2014; 723: 410–418. [CrossRef]
  • [4] Rosati A, De Masi S, Guerrini R. Antiepileptic drug treatment in children with epilepsy. CNS Drugs. 2015; 29(10): 847–863. [CrossRef]
  • [5] Kumar A, Kadian R. Levetiracetam. [Updated 2018 Apr 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan. http://www.ncbi.nlm.nih.gov/books/NBK499890 (accessed August 27, 2018).
  • [6] Drugs@FDA: FDA Approved Drug Products. http://www.accessdata.fda.gov/scripts/cder/daf/ (accessed August 27, 2018).
  • [7] FDA-Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. http://www.accessdata.fda.gov/scripts/cder/ob/ (accessed August 27, 2018).
  • [8] Fricke-Galindo I, LLerena A, Jung-Cook H, López-López M. Carbamazepine adverse drug reactions. Expert Rev Clin Pharmacol. 2018; 11(7): 705–718. [CrossRef]
  • [9] Maan JS, Saadabadi A. Carbamazepine. [Updated 2018 Jan 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan. http://www.ncbi.nlm.nih.gov/books/NBK482455 (accessed August 27, 2018).
  • [10] Sweetman SC. Martindale: The Complete Drug Reference, thirty-sixth ed. The Pharmaceutical Press, London, UK, 2009.
  • [11] Belalia F, Djelali N. Investigation of swelling/adsorption behavior of calcium alginate beads. Rev Roum Chim. 2016; 61(10): 747–754.
  • [12] Bajpai SK, Kirar N. Swelling and drug release behavior of calcium alginate/poly (sodium acrylate) hydrogel beads. Des Monomers Polym. 2016; 19(1): 89–98. [CrossRef]
  • [13] Takka S, Acartürk F. Calcium alginate microparticles for oral administration: I: effect of sodium alginate type on drug release and drug entrapment efficiency. J Microencapsul. 1999; 16(39): 275–290. [CrossRef]
  • [14] Donati I, Feresini M, Travan A, et al. Polysaccharide-based polyanion-polycation-polyanion ternary systems. A preliminary analysis of interpolyelectrolyte interactions in dilute solutions. Biomacromolecules. 2011; 12(11): 4044–4056. [CrossRef]
  • [15] Tønnesen HH, Karlsen J. Alginate in drug delivery systems. Drug Dev Ind Pharm. 2002; 28(6): 621–630. [CrossRef]
  • [16] Zohar-Perez C, Chet I, Nussinovitch A. Irregular textural features of dried alginate-filler beads. Food Hydrocoll. 2004; 18(2): 249–258. [CrossRef]
  • [17] Najafi-Soulari S, Shekarchizadeh H, Kadivar M. Encapsulation optimization of lemon balm antioxidants in calcium alginate hydrogels. J Biomater Sci Polym Ed. 2016; 27(16): 1631–1644. [CrossRef]
  • [18] El-Kamel AH, Al-Gohary OM, Hosny EA. Alginate-diltiazem hydrochloride beads: optimization of formulation factors, in vitro and in vivo availability. J Microencapsul. 2003; 20(2): 211–225. [CrossRef]
  • [19] Verma A, Sharma M, Verma N, Pandit JK. Floating alginate beads: studies on formulation factors for improved drug entrapment efficiency and in vitro release. Farmacia. 2013; 61(1): 143–161.
  • [20] Patel YL, Sher P, Pawar AP. The effect of drug concentration and curing time on processing and properties of calcium alginate beads containing metronidazole by response surface methodology. AAPS Pharm Sci Tech. 2006; 7(4): E1–E7. [CrossRef]
  • [21] Huang X, Xiao Y, Lang M. Micelles/sodium-alginate composite gel beads: A new matrix for oral drug delivery of indomethacin. Carbohydr Polym. 2012; 87(1): 790–798. [CrossRef]
  • [22] Takka S, Acartürk F. Calcium alginate microparticles for oral administration: II effect of formulation factors on drug release and drug entrapment efficiency. J Microencapsul. 1999; 16(39): 291–301. [CrossRef]
  • [23] Jao W, Ho L, Chen Z. Evaluation of the drug release mechanism of pH-sensitive calcium alginate hydrogels in simulated physiological fluids. J China Univ Sci Tech. 2010; 42: 37–61.
  • [24] Tous S, Fathy M, Fetih G, Gad SF. Preparation and evaluation of ketoprofen-loaded calcium alginate beads. Int J PharmTech Res. 2014; 6(3): 1100–1112.
  • [25] Huang X, Brazel CS. Analysis of burst release of proxyphylline from poly(vinyl alcohol) hydrogels. Chem Eng Commun. 2003; 190(4): 519–532. [CrossRef]
  • [26] Srinatha A, Pandit JK, Singh S. Ionic cross-linked chitosan beads for extended release of ciprofloxacin: in vitro characterization. Indian J Pharm Sci. 2008; 70(1): 16–21. [CrossRef]
  • [27] Huanbutta K, Nernplod T, Akkaramongkolporn P, Sriamornsak P. Design of porous Eudragit® L beads for floating drug delivery by wax removal technique. Asian J Pharm Sci. 2017; 12(3): 227–234. [CrossRef]
  • [28] Rajendran A, Basu SK. Alginate-chitosan particulate system for sustained release of nimodipine. Trop J Pharm Res. 2009; 8(5): 433–440. [CrossRef]
  • [29] Tomida H, Mizuo C, Nakamura C, Kıryu S. Imipramine release from Ca-Alginate gel beads. Chem Pharm Bull. 1993; 41(8): 1475–1477. [CrossRef]

Yıl 2019, Cilt: 23 Sayı: 4, 642 - 651, 27.06.2025

Afife Büşra Uğur Kaplan , Büşra Kandilli Meltem Çetin , Fatma Demirkaya Miloğlu

Öz

Kaynakça

  • [1] Kumar P, Jhanjee A, Bhatia MS. Lacosamide: A new antiepileptic drug. Delhi Psychiatry J. 2010; 13(2): 356–366.
  • [2] Devinsky O, Vezzani A, O’Brien TJ, et al. Epilepsy. Nat Rev Dis Primers. 2018; 3: 18024. [CrossRef]
  • [3] Florek-Luszczki M, Wlaz A, Luszczki JJ. Interactions of levetiracetam with carbamazepine, phenytoin, topiramate and vigabatrin in the mouse 6Hz psychomotor seizure model – A type II isobolographic analysis. Eur J Pharmacol. 2014; 723: 410–418. [CrossRef]
  • [4] Rosati A, De Masi S, Guerrini R. Antiepileptic drug treatment in children with epilepsy. CNS Drugs. 2015; 29(10): 847–863. [CrossRef]
  • [5] Kumar A, Kadian R. Levetiracetam. [Updated 2018 Apr 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan. http://www.ncbi.nlm.nih.gov/books/NBK499890 (accessed August 27, 2018).
  • [6] Drugs@FDA: FDA Approved Drug Products. http://www.accessdata.fda.gov/scripts/cder/daf/ (accessed August 27, 2018).
  • [7] FDA-Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. http://www.accessdata.fda.gov/scripts/cder/ob/ (accessed August 27, 2018).
  • [8] Fricke-Galindo I, LLerena A, Jung-Cook H, López-López M. Carbamazepine adverse drug reactions. Expert Rev Clin Pharmacol. 2018; 11(7): 705–718. [CrossRef]
  • [9] Maan JS, Saadabadi A. Carbamazepine. [Updated 2018 Jan 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan. http://www.ncbi.nlm.nih.gov/books/NBK482455 (accessed August 27, 2018).
  • [10] Sweetman SC. Martindale: The Complete Drug Reference, thirty-sixth ed. The Pharmaceutical Press, London, UK, 2009.
  • [11] Belalia F, Djelali N. Investigation of swelling/adsorption behavior of calcium alginate beads. Rev Roum Chim. 2016; 61(10): 747–754.
  • [12] Bajpai SK, Kirar N. Swelling and drug release behavior of calcium alginate/poly (sodium acrylate) hydrogel beads. Des Monomers Polym. 2016; 19(1): 89–98. [CrossRef]
  • [13] Takka S, Acartürk F. Calcium alginate microparticles for oral administration: I: effect of sodium alginate type on drug release and drug entrapment efficiency. J Microencapsul. 1999; 16(39): 275–290. [CrossRef]
  • [14] Donati I, Feresini M, Travan A, et al. Polysaccharide-based polyanion-polycation-polyanion ternary systems. A preliminary analysis of interpolyelectrolyte interactions in dilute solutions. Biomacromolecules. 2011; 12(11): 4044–4056. [CrossRef]
  • [15] Tønnesen HH, Karlsen J. Alginate in drug delivery systems. Drug Dev Ind Pharm. 2002; 28(6): 621–630. [CrossRef]
  • [16] Zohar-Perez C, Chet I, Nussinovitch A. Irregular textural features of dried alginate-filler beads. Food Hydrocoll. 2004; 18(2): 249–258. [CrossRef]
  • [17] Najafi-Soulari S, Shekarchizadeh H, Kadivar M. Encapsulation optimization of lemon balm antioxidants in calcium alginate hydrogels. J Biomater Sci Polym Ed. 2016; 27(16): 1631–1644. [CrossRef]
  • [18] El-Kamel AH, Al-Gohary OM, Hosny EA. Alginate-diltiazem hydrochloride beads: optimization of formulation factors, in vitro and in vivo availability. J Microencapsul. 2003; 20(2): 211–225. [CrossRef]
  • [19] Verma A, Sharma M, Verma N, Pandit JK. Floating alginate beads: studies on formulation factors for improved drug entrapment efficiency and in vitro release. Farmacia. 2013; 61(1): 143–161.
  • [20] Patel YL, Sher P, Pawar AP. The effect of drug concentration and curing time on processing and properties of calcium alginate beads containing metronidazole by response surface methodology. AAPS Pharm Sci Tech. 2006; 7(4): E1–E7. [CrossRef]
  • [21] Huang X, Xiao Y, Lang M. Micelles/sodium-alginate composite gel beads: A new matrix for oral drug delivery of indomethacin. Carbohydr Polym. 2012; 87(1): 790–798. [CrossRef]
  • [22] Takka S, Acartürk F. Calcium alginate microparticles for oral administration: II effect of formulation factors on drug release and drug entrapment efficiency. J Microencapsul. 1999; 16(39): 291–301. [CrossRef]
  • [23] Jao W, Ho L, Chen Z. Evaluation of the drug release mechanism of pH-sensitive calcium alginate hydrogels in simulated physiological fluids. J China Univ Sci Tech. 2010; 42: 37–61.
  • [24] Tous S, Fathy M, Fetih G, Gad SF. Preparation and evaluation of ketoprofen-loaded calcium alginate beads. Int J PharmTech Res. 2014; 6(3): 1100–1112.
  • [25] Huang X, Brazel CS. Analysis of burst release of proxyphylline from poly(vinyl alcohol) hydrogels. Chem Eng Commun. 2003; 190(4): 519–532. [CrossRef]
  • [26] Srinatha A, Pandit JK, Singh S. Ionic cross-linked chitosan beads for extended release of ciprofloxacin: in vitro characterization. Indian J Pharm Sci. 2008; 70(1): 16–21. [CrossRef]
  • [27] Huanbutta K, Nernplod T, Akkaramongkolporn P, Sriamornsak P. Design of porous Eudragit® L beads for floating drug delivery by wax removal technique. Asian J Pharm Sci. 2017; 12(3): 227–234. [CrossRef]
  • [28] Rajendran A, Basu SK. Alginate-chitosan particulate system for sustained release of nimodipine. Trop J Pharm Res. 2009; 8(5): 433–440. [CrossRef]
  • [29] Tomida H, Mizuo C, Nakamura C, Kıryu S. Imipramine release from Ca-Alginate gel beads. Chem Pharm Bull. 1993; 41(8): 1475–1477. [CrossRef]
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılıkta Analitik Kimya, İlaç Dağıtım Teknolojileri
Bölüm Articles
Yazarlar

Afife Büşra Uğur Kaplan

Büşra Kandilli

Meltem Çetin

Fatma Demirkaya Miloğlu

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2019 Cilt: 23 Sayı: 4

Kaynak Göster

APA Uğur Kaplan, A. B., Kandilli, B., Çetin, M., Demirkaya Miloğlu, F. (2025). Preparation and in vitro characterization of AL-Beads containing carbamazepine and/or levetiracetam. Journal of Research in Pharmacy, 23(4), 642-651.
AMA Uğur Kaplan AB, Kandilli B, Çetin M, Demirkaya Miloğlu F. Preparation and in vitro characterization of AL-Beads containing carbamazepine and/or levetiracetam. J. Res. Pharm. Haziran 2025;23(4):642-651.
Chicago Uğur Kaplan, Afife Büşra, Büşra Kandilli, Meltem Çetin, ve Fatma Demirkaya Miloğlu. “Preparation and in Vitro Characterization of AL-Beads Containing Carbamazepine and/Or Levetiracetam”. Journal of Research in Pharmacy 23, sy. 4 (Haziran 2025): 642-51.
EndNote Uğur Kaplan AB, Kandilli B, Çetin M, Demirkaya Miloğlu F (01 Haziran 2025) Preparation and in vitro characterization of AL-Beads containing carbamazepine and/or levetiracetam. Journal of Research in Pharmacy 23 4 642–651.
IEEE A. B. Uğur Kaplan, B. Kandilli, M. Çetin, ve F. Demirkaya Miloğlu, “Preparation and in vitro characterization of AL-Beads containing carbamazepine and/or levetiracetam”, J. Res. Pharm., c. 23, sy. 4, ss. 642–651, 2025.
ISNAD Uğur Kaplan, Afife Büşra vd. “Preparation and in Vitro Characterization of AL-Beads Containing Carbamazepine and/Or Levetiracetam”. Journal of Research in Pharmacy 23/4 (Haziran 2025), 642-651.
JAMA Uğur Kaplan AB, Kandilli B, Çetin M, Demirkaya Miloğlu F. Preparation and in vitro characterization of AL-Beads containing carbamazepine and/or levetiracetam. J. Res. Pharm. 2025;23:642–651.
MLA Uğur Kaplan, Afife Büşra vd. “Preparation and in Vitro Characterization of AL-Beads Containing Carbamazepine and/Or Levetiracetam”. Journal of Research in Pharmacy, c. 23, sy. 4, 2025, ss. 642-51.
Vancouver Uğur Kaplan AB, Kandilli B, Çetin M, Demirkaya Miloğlu F. Preparation and in vitro characterization of AL-Beads containing carbamazepine and/or levetiracetam. J. Res. Pharm. 2025;23(4):642-51.