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Preparation and characterization studies of etodolac suppositories: investigation on oleaginous blends of Witepsol® H15

Yıl 2023, Cilt: 27 Sayı: 2, 837 - 847, 27.06.2025

Samet Özdemir , Burcu Üner , Alptuğ Karaküçük

Öz

Etodolac is a non-steroidal anti-inflammatory drug that is categorized as a BCS class-II drug due to its low
aqueous solubility and high permeability. Frequent dosing, extensive liver metabolism, and low dissolution rates are
major limitations of etodolac. The present study focuses on the designing of novel suppository base blends for providing
an effective delivery of etodolac. The oils (Caprylic/capric triglyceride, isopropyl isostearate, and isopropyl palmitate)
were added to Witepsol® H15 to form suppository base blends. White, odorless, and torpedo-shaped suppositories were
developed by using two parts of Witepsol® H15 and one part of the oil. All of the suppositories prepared with different
blends were found uniform in weight and content. The mechanical strength of all suppositories was in an acceptable
range for suppositories (2.0 – 3.8 kg/cm2). The suppositories showed a disintegration time between 13 and 19 minutes.
First-order release kinetics were observed after the in vitro release studies. The suppository base blends released 85%-
90% of etodolac in the first hour while 60% of etodolac was released from Witepsol® H15 base alone. Prolonged drug
release was achieved after 2 hours all of the formulations reached the plateau levels. The oil blends exhibited higher
release percentages (96% - 99%) than plain Witepsol® H15 base (89%). Therefore novel suppository base blends could
be a promising formulation ingredient for the etodolac suppositories.

Anahtar Kelimeler

suppository etodolac suppository base oil Witepsol® H15

Kaynakça

  • Shah KP, Gumbhir-Shah K, Brittain HG. Etodolac, Analytical Profiles of Drug Substances and Excipients, HG Brittain, Editor. 2002; Academic Press. p. 105-147. [CrossRef]
  • Demir H, Arica-Yegin B, Oner L. Application of an artificial neural network to predict dissolution data and determine the combined effect of pH and surfactant addition on the solubility and dissolution of the weak acid drug etodolac. J Drug Deliv Sci Technol. 2018; 47: p. 215-222. [CrossRef]
  • Barakat NS. In vitro and in vivo characteristics of a thermogelling rectal delivery system of etodolac. AAPS PharmSciTech. 2009; 10(3): p. 724-31. [CrossRef]
  • Karakucuk A, Tort S, Han S, Oktay AN, Celebi N. Etodolac nanosuspension based gel for enhanced dermal delivery: in vitro and in vivo evaluation. J. Microencapsul. 2021; 38:4, 218-232. [CrossRef]
  • Salah S, Mahmoud AA, Kamel AO. Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies. Drug Deliv. 2017; 24(1), 846-856. [CrossRef]
  • Tas C, Ozkan Y, Okyar A, Savaser A. InVitro and Ex Vivo Permeation Studies of Etodolac from Hydrophilic Gels and Effect of Terpenes as Enhancers. Drug Deliv. 2007; 14:7, 453-459. [CrossRef]
  • Karakucuk A, Celebi N. Investigation of Formulation and Process Parameters of Wet Media Milling to Develop Etodolac Nanosuspensions. Pharm Res. 2020; 37, 111. [CrossRef]
  • Sarıbey G, Kahraman E, Erdal MS, Güngör S. Design and characterisation of colloidal nanocarriers for enhanced skin delivery of etodolac. J.Res.Pharm. 2021; 25(1): 22-33. [CrossRef]
  • Madhavi N, Sudhakar B, Reddy KVNS, Ratna JV. Pharmacokinetic and pharmacodynamic studies of etodolac loaded vesicular gels on rats by transdermal delivery. DARU J Pharm Sci. 2018; 26, 43–56. [CrossRef]
  • Madhavi N, Sudhakar B, Reddy KVNS, Ratna JV. Design by optimization and comparative evaluation of vesicular gels of etodolac for transdermal delivery. Drug Dev Ind Pharm. 2019; 45(4): 611-628. [CrossRef]
  • Patel DK, Kesharwani R, Kumar V. Etodolac loaded solid lipid nanoparticle based topical gel for enhanced skin delivery. Biocatal. Agric. Biotechnol. 2020; 29: 101810. [CrossRef]
  • Molina-Martinez IT, Herrero R, Gutiérrez JA, Iglesias JM, Fábregas JL, Martinez-Tobed A, Cadorniga R. Bioavailability and bioequivalence of two formulations of etodolac (tablets and suppositories). J Pharm Sci. 1993; 82(2): 211-213. [CrossRef]
  • van Hoogdalem E, de Boer AG, Breimer DD. Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs. Clin Pharmacokinet. 1991; 21(1): 11-26. [CrossRef]
  • Purohit TJ, Hanning SM, Amirapu S, Wu Z. Rectal bioavailability of amoxicillin sodium in rabbits: Effects of suppository base and drug dose. J Control Release. 2021; 338: 858-869. [CrossRef]
  • Purohit TJ, Hanning SM, Wu Z. Advances in rectal drug delivery systems. Pharm Dev Technol. 2018; 23(10): 942-952. [CrossRef]
  • Gomaa E, Abu Lila AS, Hasan AA, Ghazy F-eS. Preparation and characterization of intravaginal vardenafil suppositories targeting a complementary treatment to boost in vitro fertilization process. Eur J Pharm Sci. 2018;111: 113-20 [CrossRef]
  • Kishino T, Inoue Y, Inoue K, Saito K, Kondo M, Otsuka K, Terukina T, Hattori Y, Otsuka M. Pharmaceutical evaluation of hospital-prepared, ulinastatin-containing vaginal suppositories. J Drug Deliv Sci Technol. 2018; 44:1-7. [CrossRef]
  • Correia A, Costa CP, Silva V, Silva R, Lobo JMS, Silva AC. Pessaries containing nanostructured lipid carriers (nlc) for prolonged vaginal delivery of progesterone. Eur J Pharm Sci. 2020; 153:105475. [CrossRef]
  • Allen LV, Worthen DB, Mink B. Suppositories. 2008; Pharmaceutical Press.
  • Ghazwani M, Hani U, Osmani RAM, Rahamathulla M, Begum MY, Wahab S, Gowda DV, Ravikumar AA, Kumar HY, Ather H, Moin A. An Efficient Herbal Approach for Treating Fungal Infection in Cervical Cancer Patients by Developing and Optimizing a Vaginal Suppository. Int. J. Polym. Sci. 2021; 9198387. [CrossRef]
  • European Pharmacopoeia 10.0, Uniformity of Mass of Single-Dose Preparations, European Directorate for the Quality of Medicines & HealthCare of the Council of Europe: Strasbourg, 2022; p. 335-336.
  • Zoubari G, Staufenbiel S, Volz P, Alexiev U, Bodmeier R. Effect of drug solubility and lipid carrier on drug release from lipid nanoparticles for dermal delivery. Eur J Pharm Biopharm. 2017; 110:39-46. [CrossRef]
  • Czajkowska-Kośnik A, Szymańska E, Czarnomysy R, Jacyna J, Markuszewski M, Basa A, Winnicka K. Nanostructured Lipid Carriers Engineered as Topical Delivery of Etodolac: Optimization and Cytotoxicity Studies. Materials (Basel). 2021; 14(3):596. [CrossRef]
  • Oladiran GS, Batchelor HK. Determination of ibuprofen solubility in wax: a comparison of microscopic, thermal and release rate techniques. Eur J Pharm Biopharm. 2007; 67(1):106-11. [CrossRef]
  • Campos DA, Madureira AR, Gomes AM, Sarmento B, Pintado MM. Optimization of the production of solid Witepsol nanoparticles loaded with rosmarinic acid. Colloids Surf B Biointerfaces. 2014; 115: 109-117. [CrossRef]
  • De Muynck C, Remon JP Influence of fat composition on the melting behaviour and on the in vitro release of indomethacin suppositories. Int. J. Pharm. 1992; 85(1): 103-112. [CrossRef]
  • Amul B, Muthu S, Raja M, Sevvanthi S. Spectral, DFT and molecular docking investigations on Etodolac J. Mol. Struct. 2019; 1195: 747-761. [CrossRef]
  • Füredi P, Pápay ZE, Kovács K, Kiss BD, Ludányi K, Antal I, Klebovich I. Development and characterization of the voriconazole loaded lipid-based nanoparticles. J Pharm Biomed Anal. 2017; 132:184-189. [CrossRef]
  • Hanning SM, Matiz S, Krasser K, Orlu M, Dodoo C, Gaisford S, Tuleu C. Characterisation of rectal amoxicillin (RAMOX) for the treatment of pneumonia in children. Drug Deliv Transl Res. 2021; 11(3):944-955. [CrossRef]
  • United States Pharmacopoeia (USP43-NF38), in Etodolac Tablets. The United States Pharmacopeial Convention. 2022; p. 1787. [CrossRef]
  • United States Pharmacopoeia (USP43-NF38), in Etodolac Capsules. The United States Pharmacopeial Convention. 2022; p. 1786. [CrossRef]
  • Ozgüney I, Ozcan I, Ertan G, Güneri T. The preparation and evaluation of sustained release suppositories containing ketoprofen and Eudragit RL 100 by using factorial design. Pharm Dev Technol. 2007; 12(1):97-107. [CrossRef]
  • Uzunkaya G, Bergişadi N. In vitro drug liberation and kinetics of sustained release indomethacin suppository. Farmaco. 2003; 58(7):509-512. [CrossRef]
  • Saleem MA, Taher M, Sanaullah S, Najmuddin M, Ali J, Humaira S, Roshan S. Formulation and Evaluation of Tramadol hydrochloride Rectal Suppositories. Indian J Pharm Sci. 2008; 70(5):640-644. [CrossRef]
  • Jin YX, Tang YH, Zeng S. Analysis of flurbiprofen, ketoprofen and etodolac enantiomers by pre-column derivatization RP-HPLC and application to drug-protein binding in human plasma. J Pharm Biomed Anal. 2008; 46(5): 953-958. [CrossRef]
  • European Pharmacopoeia 10.0, Uniformity of The Content of Single-Dose Preparations. European Directorate for the Quality of Medicines & HealthCare of the Council of Europe: Strasbourg. 2022; p. 336-337.
  • Üner B, Özdemir S, Taş Ç, Özsoy Y, Üner M. Development of lipid nanoparticles for transdermal loteprednol etabonate delivery. J Microencapsul. 2022; 39(4): 327-340. [CrossRef]
  • European Pharmacopoeia 10.0, Disintegration of Tablets and Capsules. 2022, European Directorate for the Quality of Medicines & HealthCare of the Council of Europe: Strasbourg. 2022; p. 5995-5997.
  • Abd-Elbary A, Tadros MI, Alaa-Eldin AA. Sucrose stearate-enriched lipid matrix tablets of etodolac: modulation of drug release, diffusional modeling and structure elucidation studies. AAPS PharmSciTech. 2013; 14(2):656-68. [CrossRef]
  • Üner M, Karaman EF. Preliminary studies on solid lipid microparticles of loratadine for the treatment of allergic reactions via the nasal route. Trop. J. Pharm. Res. 2013; 12(3):287-93 [CrossRef]

Yıl 2023, Cilt: 27 Sayı: 2, 837 - 847, 27.06.2025

Samet Özdemir , Burcu Üner , Alptuğ Karaküçük

Öz

Kaynakça

  • Shah KP, Gumbhir-Shah K, Brittain HG. Etodolac, Analytical Profiles of Drug Substances and Excipients, HG Brittain, Editor. 2002; Academic Press. p. 105-147. [CrossRef]
  • Demir H, Arica-Yegin B, Oner L. Application of an artificial neural network to predict dissolution data and determine the combined effect of pH and surfactant addition on the solubility and dissolution of the weak acid drug etodolac. J Drug Deliv Sci Technol. 2018; 47: p. 215-222. [CrossRef]
  • Barakat NS. In vitro and in vivo characteristics of a thermogelling rectal delivery system of etodolac. AAPS PharmSciTech. 2009; 10(3): p. 724-31. [CrossRef]
  • Karakucuk A, Tort S, Han S, Oktay AN, Celebi N. Etodolac nanosuspension based gel for enhanced dermal delivery: in vitro and in vivo evaluation. J. Microencapsul. 2021; 38:4, 218-232. [CrossRef]
  • Salah S, Mahmoud AA, Kamel AO. Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies. Drug Deliv. 2017; 24(1), 846-856. [CrossRef]
  • Tas C, Ozkan Y, Okyar A, Savaser A. InVitro and Ex Vivo Permeation Studies of Etodolac from Hydrophilic Gels and Effect of Terpenes as Enhancers. Drug Deliv. 2007; 14:7, 453-459. [CrossRef]
  • Karakucuk A, Celebi N. Investigation of Formulation and Process Parameters of Wet Media Milling to Develop Etodolac Nanosuspensions. Pharm Res. 2020; 37, 111. [CrossRef]
  • Sarıbey G, Kahraman E, Erdal MS, Güngör S. Design and characterisation of colloidal nanocarriers for enhanced skin delivery of etodolac. J.Res.Pharm. 2021; 25(1): 22-33. [CrossRef]
  • Madhavi N, Sudhakar B, Reddy KVNS, Ratna JV. Pharmacokinetic and pharmacodynamic studies of etodolac loaded vesicular gels on rats by transdermal delivery. DARU J Pharm Sci. 2018; 26, 43–56. [CrossRef]
  • Madhavi N, Sudhakar B, Reddy KVNS, Ratna JV. Design by optimization and comparative evaluation of vesicular gels of etodolac for transdermal delivery. Drug Dev Ind Pharm. 2019; 45(4): 611-628. [CrossRef]
  • Patel DK, Kesharwani R, Kumar V. Etodolac loaded solid lipid nanoparticle based topical gel for enhanced skin delivery. Biocatal. Agric. Biotechnol. 2020; 29: 101810. [CrossRef]
  • Molina-Martinez IT, Herrero R, Gutiérrez JA, Iglesias JM, Fábregas JL, Martinez-Tobed A, Cadorniga R. Bioavailability and bioequivalence of two formulations of etodolac (tablets and suppositories). J Pharm Sci. 1993; 82(2): 211-213. [CrossRef]
  • van Hoogdalem E, de Boer AG, Breimer DD. Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs. Clin Pharmacokinet. 1991; 21(1): 11-26. [CrossRef]
  • Purohit TJ, Hanning SM, Amirapu S, Wu Z. Rectal bioavailability of amoxicillin sodium in rabbits: Effects of suppository base and drug dose. J Control Release. 2021; 338: 858-869. [CrossRef]
  • Purohit TJ, Hanning SM, Wu Z. Advances in rectal drug delivery systems. Pharm Dev Technol. 2018; 23(10): 942-952. [CrossRef]
  • Gomaa E, Abu Lila AS, Hasan AA, Ghazy F-eS. Preparation and characterization of intravaginal vardenafil suppositories targeting a complementary treatment to boost in vitro fertilization process. Eur J Pharm Sci. 2018;111: 113-20 [CrossRef]
  • Kishino T, Inoue Y, Inoue K, Saito K, Kondo M, Otsuka K, Terukina T, Hattori Y, Otsuka M. Pharmaceutical evaluation of hospital-prepared, ulinastatin-containing vaginal suppositories. J Drug Deliv Sci Technol. 2018; 44:1-7. [CrossRef]
  • Correia A, Costa CP, Silva V, Silva R, Lobo JMS, Silva AC. Pessaries containing nanostructured lipid carriers (nlc) for prolonged vaginal delivery of progesterone. Eur J Pharm Sci. 2020; 153:105475. [CrossRef]
  • Allen LV, Worthen DB, Mink B. Suppositories. 2008; Pharmaceutical Press.
  • Ghazwani M, Hani U, Osmani RAM, Rahamathulla M, Begum MY, Wahab S, Gowda DV, Ravikumar AA, Kumar HY, Ather H, Moin A. An Efficient Herbal Approach for Treating Fungal Infection in Cervical Cancer Patients by Developing and Optimizing a Vaginal Suppository. Int. J. Polym. Sci. 2021; 9198387. [CrossRef]
  • European Pharmacopoeia 10.0, Uniformity of Mass of Single-Dose Preparations, European Directorate for the Quality of Medicines & HealthCare of the Council of Europe: Strasbourg, 2022; p. 335-336.
  • Zoubari G, Staufenbiel S, Volz P, Alexiev U, Bodmeier R. Effect of drug solubility and lipid carrier on drug release from lipid nanoparticles for dermal delivery. Eur J Pharm Biopharm. 2017; 110:39-46. [CrossRef]
  • Czajkowska-Kośnik A, Szymańska E, Czarnomysy R, Jacyna J, Markuszewski M, Basa A, Winnicka K. Nanostructured Lipid Carriers Engineered as Topical Delivery of Etodolac: Optimization and Cytotoxicity Studies. Materials (Basel). 2021; 14(3):596. [CrossRef]
  • Oladiran GS, Batchelor HK. Determination of ibuprofen solubility in wax: a comparison of microscopic, thermal and release rate techniques. Eur J Pharm Biopharm. 2007; 67(1):106-11. [CrossRef]
  • Campos DA, Madureira AR, Gomes AM, Sarmento B, Pintado MM. Optimization of the production of solid Witepsol nanoparticles loaded with rosmarinic acid. Colloids Surf B Biointerfaces. 2014; 115: 109-117. [CrossRef]
  • De Muynck C, Remon JP Influence of fat composition on the melting behaviour and on the in vitro release of indomethacin suppositories. Int. J. Pharm. 1992; 85(1): 103-112. [CrossRef]
  • Amul B, Muthu S, Raja M, Sevvanthi S. Spectral, DFT and molecular docking investigations on Etodolac J. Mol. Struct. 2019; 1195: 747-761. [CrossRef]
  • Füredi P, Pápay ZE, Kovács K, Kiss BD, Ludányi K, Antal I, Klebovich I. Development and characterization of the voriconazole loaded lipid-based nanoparticles. J Pharm Biomed Anal. 2017; 132:184-189. [CrossRef]
  • Hanning SM, Matiz S, Krasser K, Orlu M, Dodoo C, Gaisford S, Tuleu C. Characterisation of rectal amoxicillin (RAMOX) for the treatment of pneumonia in children. Drug Deliv Transl Res. 2021; 11(3):944-955. [CrossRef]
  • United States Pharmacopoeia (USP43-NF38), in Etodolac Tablets. The United States Pharmacopeial Convention. 2022; p. 1787. [CrossRef]
  • United States Pharmacopoeia (USP43-NF38), in Etodolac Capsules. The United States Pharmacopeial Convention. 2022; p. 1786. [CrossRef]
  • Ozgüney I, Ozcan I, Ertan G, Güneri T. The preparation and evaluation of sustained release suppositories containing ketoprofen and Eudragit RL 100 by using factorial design. Pharm Dev Technol. 2007; 12(1):97-107. [CrossRef]
  • Uzunkaya G, Bergişadi N. In vitro drug liberation and kinetics of sustained release indomethacin suppository. Farmaco. 2003; 58(7):509-512. [CrossRef]
  • Saleem MA, Taher M, Sanaullah S, Najmuddin M, Ali J, Humaira S, Roshan S. Formulation and Evaluation of Tramadol hydrochloride Rectal Suppositories. Indian J Pharm Sci. 2008; 70(5):640-644. [CrossRef]
  • Jin YX, Tang YH, Zeng S. Analysis of flurbiprofen, ketoprofen and etodolac enantiomers by pre-column derivatization RP-HPLC and application to drug-protein binding in human plasma. J Pharm Biomed Anal. 2008; 46(5): 953-958. [CrossRef]
  • European Pharmacopoeia 10.0, Uniformity of The Content of Single-Dose Preparations. European Directorate for the Quality of Medicines & HealthCare of the Council of Europe: Strasbourg. 2022; p. 336-337.
  • Üner B, Özdemir S, Taş Ç, Özsoy Y, Üner M. Development of lipid nanoparticles for transdermal loteprednol etabonate delivery. J Microencapsul. 2022; 39(4): 327-340. [CrossRef]
  • European Pharmacopoeia 10.0, Disintegration of Tablets and Capsules. 2022, European Directorate for the Quality of Medicines & HealthCare of the Council of Europe: Strasbourg. 2022; p. 5995-5997.
  • Abd-Elbary A, Tadros MI, Alaa-Eldin AA. Sucrose stearate-enriched lipid matrix tablets of etodolac: modulation of drug release, diffusional modeling and structure elucidation studies. AAPS PharmSciTech. 2013; 14(2):656-68. [CrossRef]
  • Üner M, Karaman EF. Preliminary studies on solid lipid microparticles of loratadine for the treatment of allergic reactions via the nasal route. Trop. J. Pharm. Res. 2013; 12(3):287-93 [CrossRef]
Toplam 40 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Biyoteknoloji
Bölüm Articles
Yazarlar

Samet Özdemir 0000-0001-6212-2706

Burcu Üner 0000-0003-4691-0432

Alptuğ Karaküçük 0000-0002-9061-2427

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 2

Kaynak Göster

APA Özdemir, S., Üner, B., & Karaküçük, A. (2025). Preparation and characterization studies of etodolac suppositories: investigation on oleaginous blends of Witepsol® H15. Journal of Research in Pharmacy, 27(2), 837-847.
AMA Özdemir S, Üner B, Karaküçük A. Preparation and characterization studies of etodolac suppositories: investigation on oleaginous blends of Witepsol® H15. J. Res. Pharm. Haziran 2025;27(2):837-847.
Chicago Özdemir, Samet, Burcu Üner, ve Alptuğ Karaküçük. “Preparation and Characterization Studies of Etodolac Suppositories: Investigation on Oleaginous Blends of Witepsol® H15”. Journal of Research in Pharmacy 27, sy. 2 (Haziran 2025): 837-47.
EndNote Özdemir S, Üner B, Karaküçük A (01 Haziran 2025) Preparation and characterization studies of etodolac suppositories: investigation on oleaginous blends of Witepsol® H15. Journal of Research in Pharmacy 27 2 837–847.
IEEE S. Özdemir, B. Üner, ve A. Karaküçük, “Preparation and characterization studies of etodolac suppositories: investigation on oleaginous blends of Witepsol® H15”, J. Res. Pharm., c. 27, sy. 2, ss. 837–847, 2025.
ISNAD Özdemir, Samet vd. “Preparation and Characterization Studies of Etodolac Suppositories: Investigation on Oleaginous Blends of Witepsol® H15”. Journal of Research in Pharmacy 27/2 (Haziran 2025), 837-847.
JAMA Özdemir S, Üner B, Karaküçük A. Preparation and characterization studies of etodolac suppositories: investigation on oleaginous blends of Witepsol® H15. J. Res. Pharm. 2025;27:837–847.
MLA Özdemir, Samet vd. “Preparation and Characterization Studies of Etodolac Suppositories: Investigation on Oleaginous Blends of Witepsol® H15”. Journal of Research in Pharmacy, c. 27, sy. 2, 2025, ss. 837-4.
Vancouver Özdemir S, Üner B, Karaküçük A. Preparation and characterization studies of etodolac suppositories: investigation on oleaginous blends of Witepsol® H15. J. Res. Pharm. 2025;27(2):837-4.