Formulation development of Lornoxicam loaded heat triggered ocular in-situ gel using factorial design


Polat H. K., ÜNAL S., AYTEKİN E., KARAKUYU N. F., PEZİK E., HAYDAR M. K., ...Daha Fazla

Drug Development and Industrial Pharmacy, cilt.49, sa.9, ss.601-615, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 49 Sayı: 9
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1080/03639045.2023.2264932
  • Dergi Adı: Drug Development and Industrial Pharmacy
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, Business Source Elite, Business Source Premier, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, Veterinary Science Database
  • Sayfa Sayıları: ss.601-615
  • Anahtar Kelimeler: cell viability, cyclodextrin, draize test, Lornoxicam, release kinetic
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Objective: In the current research, lornoxicam-loaded in situ gels were developed, and their potential usage in ocular inflammation was evaluated. Significance: Lornoxicam cyclodextrin complex prepared with hydroxypropyl methylcellulose and poloxamer P407 because of the low viscosity of in situ gels to provide easy application. However, washing and removing it from the ocular surface becomes difficult due to the gelation formation with heat. Methods: A three-level factorial experimental design was used to evaluate the effects of poloxamer 407 concentration, polymer type, and polymer concentration on viscosity, pH, gelation capacity, gelation time, and gelation temperature, which were considered the optimal indicators of lornoxicam-containing formulations. Results: As a result of the three-level factorial experimental design, the optimized formulation contained 15 (%w/v) poloxamer 407 and 1 (%w/v) hydroxypropyl methylcellulose. The optimize formulation viscosity 25 °C = 504 ± 49cP, viscosity 35 °C = 11247 ± 214cP, pH = 6.80 ± 0.01, gelation temprature = 35 ± 0.2 °C, and gelation time= 34 ± 0.2 s was obtained. In the in vitro release studies, 68% of lornoxicam was released with a burst effect in the first three hours; then, the release continued for eight hours with controlled release. Release kinetics of the formulations were modeled mathematically, and it was found to be compatible with the Korsemeyer-Peppas and Weibull models. In cell culture studies, cell viability at 100 µg/mL was 83% and 96% for NL6 and NL6-CD, respectively. In Draize’s in vivo test, no negative conditions occurred in rats. Conclusions: Therefore, the NL6-CD formulation has the potential to be a favorable option for treating ocular inflammation.