Araştırma Makalesi
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Design of Thymol Loaded Dental In Situ Gels; In Vitro Evaluation

Yıl 2022, Cilt: 13 Sayı: 3, 475 - 484, 20.12.2022
https://doi.org/10.22312/sdusbed.1150492

Öz

Objetive: The aim of the study was to develop thymol thermosensitive in situ gels based on poloxamers in order to prolong dental contact time, control drug release, and enhance dental bioavailability.
Materials and Methods: Poloxamer 188 (P188) and poloxamer 407 (P407) were used in varying amounts to designed the in situ gels. Mucoadhesive excipient, like hydroxypropyl methylcellulose (HPMC), was transferred to the in situ gels to improve the formulation's ability to adhere to biological surfaces. For the created formulations, in vitro drug release, pH, clarity, and sol-gel transition temperature were all evaluated.
Results: The all of in situ gels gelation temperatures of the developed formulations range from 33 to 37°C, pH values are around 7, and syringeability is defined as the amount of force necessary to discharge each formulation from a syringe fitted with a 20-gauge needle. The quantities of P407 and HPMC with the preparations, decreasing in vitro burst release while also increasing the viscosity but every in situ gel formulation releases for six hours.
Conclusion:The results show that in situ gels containing P407 and P188 show promise for thymol dental application.

Kaynakça

  • [1]. Pihlstrom BL, Michalowicz BS, Johnson NW. 2005. Periodontal diseases. The Lancet,366(9499),1809-20.
  • [2]. Babu J, Ayyappan T, Vetrichelvan T. 2011. Novel site specific delivery system containing ofloxacin for the treatment of periodontal infection. Research Journal of Pharmaceutical, Biological and Chemical Sciences .2,590-602.
  • [3]. Garala K, Joshi P, Shah M, Ramkishan A, Patel J. 2013.Formulation and evaluation of periodontal in situ gel. International Journal of Pharmaceutical Investigation.,3(1),29.
  • [4]. Mueller-Riebau F, Berger B, Yegen O. 1995.Chemical composition and fungitoxic properties to phytopathogenic fungi of essential oils of selected aromatic plants growing wild in Turkey. Journal of Agricultural and Food Chemistry.43(8),2262-6.
  • [5]. Aksit H, Bayar Y, Simsek S, Ulutas Y. 2022.Chemical Composition and Antifungal Activities of the Essential Oils of Thymus Species (Thymus pectinatus, Thymus convolutus, Thymus vulgaris) Against Plant Pathogens. Journal of Essential Oil Bearing Plants.,25(1),200-7.
  • [6]. Braga PC, Dal Sasso M, Culici M, Bianchi T, Bordoni L, Marabini L. 2006. Anti-inflammatory activity of thymol: inhibitory effect on the release of human neutrophil elastase. Pharmacology.,77(3),130-6.
  • [7]. Ivanovic J, Misic D, Zizovic I, Ristic M. 2012.In vitro control of multiplication of some food-associated bacteria by thyme, rosemary and sage isolates. Food Control.,25(1),110-6.
  • [8]. Tian H, Lai D. 2006. Analysis on the volatile oil in Origanum vulgare. Zhong yao cai= Zhongyaocai= Journal of Chinese Medicinal Materials.,29(9),920-1.
  • [9]. Nabavi SM, Marchese A, Izadi M, Curti V, Daglia M, Nabavi SF. 2015.Plants belonging to the genus Thymus as antibacterial agents: From farm to pharmacy. Food Chemistry.,173,339-47.
  • [10]. Patole VC, Chaudhari SP. 2021.Development of Thymol Microsponges Loaded in situ Gel for the Treatment of Periodontitis. Current Drug Delivery.,18(1),71-87.
  • [11]. Embuscado ME. 2015.Spices and herbs: Natural sources of antioxidants–a mini review. Journal of Functional Foods.,18,811-9.
  • [12]. Nasra MM, Khiri HM, Hazzah HA, Abdallah OY. 2017. Formulation, in-vitro characterization and clinical evaluation of curcumin in-situ gel for treatment of periodontitis. Drug Delivery.,24(1),133-42.
  • [13]. Salager E, Stein RS, Pickard CJ, Elena B, Emsley L. 2009. Powder NMR crystallography of thymol. Physical Chemistry Chemical Physics.,11(15),2610-21.
  • [14]. Schmolka IR. Artificial skin I. 1972. Preparation and properties of pluronic F‐127 gels for treatment of burns. Journal of Biomedical Materials Research.,6(6),571-82.
  • [15]. Ribeiro A, Figueiras A, Santos D, Veiga F. 2008.Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl-β-cyclodextrin. AAPS Pharmscitech.,9(4),1102-9.
  • [16]. Maheshwari M, Miglani G, Mali A, Paradkar A, Yamamura S, Kadam S. 2006.Development of tetracycline-serratiopeptidase-containing periodontal gel: formulation and preliminary clinical study. AAPS PharmSciTech.,7(3),E162-E71.
  • [17]. Alexandridis P, Hatton TA. 1995. Poly (ethylene oxide) poly (propylene oxide) poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling. Colloids and Surfaces A: Physicochemical and Engineering Aspects.,96(1-2),1-46.
  • [18]. Zhang, Y., Zhang, Y., Zhu, Z., Jiao, X., Shang, Y., & Wen, Y. 2019. Encapsulation of thymol in biodegradable nanofiber via coaxial eletrospinning and applications in fruit preservation. Journal of Agricultural and Food Chemistry, 67(6), 1736-1741.
  • [19]. Lade B, Kamdi A, Shanware A. 2021. Enhanced Antibacterial and Antioxidant Properties of Chitosan Films Blended with Gallic Acid and Incorporated with Thymol Silver Nanoparticles. Journal of Drug Delivery and Therapeutics.,11(6-S),53-69.
  • [20]. Karataş A, Sonakin O, KiliÇarslan M, Baykara T. 2009. Poly (ε-caprolactone) microparticles containing levobunolol HCl prepared by a multiple emulsion (W/O/W) solvent evaporation technique: Effects of some formulation parameters on microparticle characteristics. Journal of Microencapsulation.,26(1),63-74.
  • [21]. Pham DT, Phewchan P, Navesit K, Chokamonsirikun A, Khemwong T, Tiyaboonchai W.2021. Development of metronidazole-loaded in situ thermosensitive hydrogel for periodontitis treatment. Turkish Journal of Pharmaceutical Sciences.,18(4),510.
  • [22]. Gilbert JC, Richardson JL, Davies MC, Palin KJ, Hadgraft J. 1987The effect of solutes and polymers on the gelation properties of pluronic F-127 solutions for controlled drug delivery. Journal of cControlled rRelease.,5(2),113-8.
  • [23]. Benoliel, R., & Sharav, Y. 2008. Masticatory myofascial pain, and tension-type and chronic daily headache. Orofacial pain and headache. Edinburgh: Elsevier, 109-28.
  • [24]. Fathalla ZM, Vangala A, Longman M, Khaled KA, Hussein AK, El-Garhy OH, et al. 2017. Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies. European Journal of Pharmaceutics and Biopharmaceutics.,114,119-34 . [25]. Schmolka IR. 1991 Poloxamers in the pharmaceutical industry: CRC Press: Boca Raton, FL, USA.
  • [26]. El-Kamel 2002.A. In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate. International Journal of Pharmaceutics,241(1),47-55.

Timol Yüklü Diş İn Situ Jellerin Tasarımı; In Vitro Değerlendirilmesi

Yıl 2022, Cilt: 13 Sayı: 3, 475 - 484, 20.12.2022
https://doi.org/10.22312/sdusbed.1150492

Öz

Amaç: Bu çalışmanın amacı, dental temas süresini uzatmak, ilaç salımını kontrol etmek ve dental biyoyararlanımı arttırmak için poloksamerlere dayalı timol yüklü in situ jel formülasyonları geliştirmektir.
Gereç ve Yöntem: İn situ jellerin tasarımında Poloksamer 188 (P188) ve Poloksamer 407 (P407) farklı oranlarda kullanılmıştır. Jelin biyolojik yüzeylere yapışma yeteneğini geliştirmek için formülasyonlara hidroksipropil metilselüloz (HPMC) gibi muko-yapışkan bir yardımcı madde eklenmiştir. Oluşturulan formülasyonlar için in vitro ilaç salımı, pH, berraklık ve sol-jel geçiş sıcaklığı değerlendirilmiştir.
Bulgular: Geliştirilen formülasyonların jelleşme sıcaklıkları 33 ila 37°C arasında olduğu, pH değerlerinin yaklaşık 7 olduğu ve 20 numaralı iğne ile şırıngalanabilir olduğu görülmüştür. Preparat içerisindeki, P407 ve HPMC miktarları yükseldikçe, in vitro patlama salım azalırken aynı zamanda viskozitenin arttığı tespit edilmiştir, bütün in situ jel formülasyonlarının altı saat süre ile salım yaptığı belirlenmiştir.
Sonuç: Sonuçlar, timol içeren P407 ve P188 in situ jellerin timol diş uygulaması için umut verici olduğunu göstermektedir.

Kaynakça

  • [1]. Pihlstrom BL, Michalowicz BS, Johnson NW. 2005. Periodontal diseases. The Lancet,366(9499),1809-20.
  • [2]. Babu J, Ayyappan T, Vetrichelvan T. 2011. Novel site specific delivery system containing ofloxacin for the treatment of periodontal infection. Research Journal of Pharmaceutical, Biological and Chemical Sciences .2,590-602.
  • [3]. Garala K, Joshi P, Shah M, Ramkishan A, Patel J. 2013.Formulation and evaluation of periodontal in situ gel. International Journal of Pharmaceutical Investigation.,3(1),29.
  • [4]. Mueller-Riebau F, Berger B, Yegen O. 1995.Chemical composition and fungitoxic properties to phytopathogenic fungi of essential oils of selected aromatic plants growing wild in Turkey. Journal of Agricultural and Food Chemistry.43(8),2262-6.
  • [5]. Aksit H, Bayar Y, Simsek S, Ulutas Y. 2022.Chemical Composition and Antifungal Activities of the Essential Oils of Thymus Species (Thymus pectinatus, Thymus convolutus, Thymus vulgaris) Against Plant Pathogens. Journal of Essential Oil Bearing Plants.,25(1),200-7.
  • [6]. Braga PC, Dal Sasso M, Culici M, Bianchi T, Bordoni L, Marabini L. 2006. Anti-inflammatory activity of thymol: inhibitory effect on the release of human neutrophil elastase. Pharmacology.,77(3),130-6.
  • [7]. Ivanovic J, Misic D, Zizovic I, Ristic M. 2012.In vitro control of multiplication of some food-associated bacteria by thyme, rosemary and sage isolates. Food Control.,25(1),110-6.
  • [8]. Tian H, Lai D. 2006. Analysis on the volatile oil in Origanum vulgare. Zhong yao cai= Zhongyaocai= Journal of Chinese Medicinal Materials.,29(9),920-1.
  • [9]. Nabavi SM, Marchese A, Izadi M, Curti V, Daglia M, Nabavi SF. 2015.Plants belonging to the genus Thymus as antibacterial agents: From farm to pharmacy. Food Chemistry.,173,339-47.
  • [10]. Patole VC, Chaudhari SP. 2021.Development of Thymol Microsponges Loaded in situ Gel for the Treatment of Periodontitis. Current Drug Delivery.,18(1),71-87.
  • [11]. Embuscado ME. 2015.Spices and herbs: Natural sources of antioxidants–a mini review. Journal of Functional Foods.,18,811-9.
  • [12]. Nasra MM, Khiri HM, Hazzah HA, Abdallah OY. 2017. Formulation, in-vitro characterization and clinical evaluation of curcumin in-situ gel for treatment of periodontitis. Drug Delivery.,24(1),133-42.
  • [13]. Salager E, Stein RS, Pickard CJ, Elena B, Emsley L. 2009. Powder NMR crystallography of thymol. Physical Chemistry Chemical Physics.,11(15),2610-21.
  • [14]. Schmolka IR. Artificial skin I. 1972. Preparation and properties of pluronic F‐127 gels for treatment of burns. Journal of Biomedical Materials Research.,6(6),571-82.
  • [15]. Ribeiro A, Figueiras A, Santos D, Veiga F. 2008.Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl-β-cyclodextrin. AAPS Pharmscitech.,9(4),1102-9.
  • [16]. Maheshwari M, Miglani G, Mali A, Paradkar A, Yamamura S, Kadam S. 2006.Development of tetracycline-serratiopeptidase-containing periodontal gel: formulation and preliminary clinical study. AAPS PharmSciTech.,7(3),E162-E71.
  • [17]. Alexandridis P, Hatton TA. 1995. Poly (ethylene oxide) poly (propylene oxide) poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling. Colloids and Surfaces A: Physicochemical and Engineering Aspects.,96(1-2),1-46.
  • [18]. Zhang, Y., Zhang, Y., Zhu, Z., Jiao, X., Shang, Y., & Wen, Y. 2019. Encapsulation of thymol in biodegradable nanofiber via coaxial eletrospinning and applications in fruit preservation. Journal of Agricultural and Food Chemistry, 67(6), 1736-1741.
  • [19]. Lade B, Kamdi A, Shanware A. 2021. Enhanced Antibacterial and Antioxidant Properties of Chitosan Films Blended with Gallic Acid and Incorporated with Thymol Silver Nanoparticles. Journal of Drug Delivery and Therapeutics.,11(6-S),53-69.
  • [20]. Karataş A, Sonakin O, KiliÇarslan M, Baykara T. 2009. Poly (ε-caprolactone) microparticles containing levobunolol HCl prepared by a multiple emulsion (W/O/W) solvent evaporation technique: Effects of some formulation parameters on microparticle characteristics. Journal of Microencapsulation.,26(1),63-74.
  • [21]. Pham DT, Phewchan P, Navesit K, Chokamonsirikun A, Khemwong T, Tiyaboonchai W.2021. Development of metronidazole-loaded in situ thermosensitive hydrogel for periodontitis treatment. Turkish Journal of Pharmaceutical Sciences.,18(4),510.
  • [22]. Gilbert JC, Richardson JL, Davies MC, Palin KJ, Hadgraft J. 1987The effect of solutes and polymers on the gelation properties of pluronic F-127 solutions for controlled drug delivery. Journal of cControlled rRelease.,5(2),113-8.
  • [23]. Benoliel, R., & Sharav, Y. 2008. Masticatory myofascial pain, and tension-type and chronic daily headache. Orofacial pain and headache. Edinburgh: Elsevier, 109-28.
  • [24]. Fathalla ZM, Vangala A, Longman M, Khaled KA, Hussein AK, El-Garhy OH, et al. 2017. Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies. European Journal of Pharmaceutics and Biopharmaceutics.,114,119-34 . [25]. Schmolka IR. 1991 Poloxamers in the pharmaceutical industry: CRC Press: Boca Raton, FL, USA.
  • [26]. El-Kamel 2002.A. In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate. International Journal of Pharmaceutics,241(1),47-55.
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Heybet Kerem Polat 0000-0001-5006-3091

Sefa Gözcü 0000-0002-0735-4229

Hüseyin Akşit 0000-0002-1509-851X

Yayımlanma Tarihi 20 Aralık 2022
Gönderilme Tarihi 29 Temmuz 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 13 Sayı: 3

Kaynak Göster

Vancouver Polat HK, Gözcü S, Akşit H. Design of Thymol Loaded Dental In Situ Gels; In Vitro Evaluation. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi. 2022;13(3):475-84.

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