Neslihan ÜSTÜNDAĞ OKUR, Gizem YEĞEN, Buket AKSU, Mohammed KALAYI

Evaluation of emulgel formulations contain diclofenac sodium via quality by design approach

Emulgel is considered as emulsions, either oil-in-water or water-in-oil type, that is formed via blending with a gelling agent. Their common usage as pharmaceutical dosage form results from the broad utilization of emulsion systems, particularly for dermatological formulations. Quality by Design (QbD) is a scientific, holistic, risk-based, systematic, and proactive approach that starts with predefined objectives and assertiveness on product quality, procedure understanding, and process control. In this study, the QbD approach was implemented in the production of emulgel containing diclofenac sodium and the goal was to build quality into the product from the inception of formulation development. The hydrogel phase and oil phase of emulgel were prepared separately, then mixed. Emulgels were evaluated for their macroscopic, and microscopic examination, pH, electrical conductivity measurements, and viscosity. The optimum formulation was found by using the ANN Modelling program. According to macroscopic evaluation the optimum emulgel was an opaque white color, and homogeneous with no phase separation or grittiness. The viscosity of the optimum formula is 4600, pH value is 6.7, electrical conductivity is 120 μS-1, and particle diameter was also 0,989 μm. Results showed the optimized formula has the required properties. ANN modeling technique has been used to develop a pharmaceutical formulation via determining multivariate relations between independent parameters and quality properties affected by these parameters. Although artificial intelligence programs are not enough to build and develop formulations by itself, they play a significant role in formulation development.

PDF

___

[1] Baviskar D, Biranwar Y, Bare K, Parik V, Sapate M, Jain D. In Vitro and in vivo evaluation of diclofenac sodium gelprepared with cellulose ether and carbopol 934p. Trop J Pharm Res. 2013; 12(4): 489-494. [CrossRef]
[2] Allen L,Ansels Pharmaceutical Dosage Forms And Drug Delivery Systems, eleventh ed.,Lippincott Williams and Wilkins, Philadelphia, USA 2017.
[3] Kumar D, Singh J, Antil M, Kumar V. Emulgel-novel topical drug delivery system–a comprehensive review. Int J Pharm Sci Res. 2016; 7(12): 4733-4742. [CrossRef]
[4] Khullar R, Kumar D, Seth N,Saini S. Formulation and evaluation of mefenamic acid emulgel for topical delivery. Saudi Pharm J. 2012; 20(1): 63-67. [CrossRef]
[5] Suresh S, Roy S, Ahuja BK. Quality by design: an overview. Indian Drugs. 2015; 52(02): 5-11[CrossRef]
[6] Aksu B, Mesut B. Quality by design (QbD) for pharmaceutical area. Istanbul J Pharm. 2015; 45(2): 233-251.
[7] Aksu NB, Yozgatlı V, Okur ME, Ayla Ş, Yoltaş A, Okur NÜ. Preparation and evaluation OF QBD based fusidic acid loaded in situ gel formulations for burn wound treatment. J Drug Deliv Sci Technol. 2019; 52: 110-121. [CrossRef]
[8] Aksu B, Coşkunmerıç N, Yeğen G, Özalp Y, Okur NÜ. Quality by design approach for optimizingPreparation and characterization of buccal film formulation with different polymers. IntJPharmRes. 2019; 11(1): 1153-1160. [CrossRef]
[9] Aksu B, Yeğen G. Benefits of computerized technologies in pharmaceutical development with quality by design approach.J Comput Eng Inf Technol. 2017;6(1).[CrossRef]
[10] Yurdasiper A, Aksu B, Üstündağ Okur N, Gokce E. An optimization study on solid lipid nanoparticles using artificial neural network. LatAm J Pharm.2017; 36(1): 115-121.
[11] Plumb AP, Rowe RC, York P, Brown M. Optimisation of the predictive ability of artificial neural network (ANN) models: A comparison of three ANN programs and four classes of training algorithm. EurJPharmSci.2005;25(4-5): 395–405.[CrossRef]
[12] Mwangi AN, Njogu PM, Maru SM, Njuguna NM, Njaria PM, Kiriiri KG, Mathenge AW. Meloxicam emulgels for topical management of rheumatism: Formulation development, in vitro and in vivo characterization. Saudi Pharm J. 2021; 29(4): 351–360. [CrossRef]
[13] Yapar EA, İnal Ö, Erdal MS. Design and in vivo evaluation of emulgel formulationsincluding green tea extract and rose oil. Acta Pharm. 2013; 63(4):531–543.[CrossRef]
[14] Khullar R, Kumar D, Seth N, Saini S. Formulation and evaluation of mefenamic acid emulgel for topical delivery. Saudi Pharm J. 2012; 20(1): 63–67.[CrossRef]
[15] Yılmaz G, Tanrıverdi Tuncay S, Aksu B, Yeğen G, Özer O. Preparation and in vitro characterization of etofenamate emulgels using quality by design. J Res Pharm. 2019; 23(6): 1033-1039.[CrossRef]
[16] Mohite S, Salunkhe A. Formulation and evaluation of Emulgel containing Coriandrum sativum seeds oil for Antiinflammatory activity.J Drug Delivery Ther. 2019; 9(3-s):124-130. [CrossRef]
[17] Burki I K, Khan M K, Khan B A, Uzair B, Braga V A, Jamil Q A. Formulation development, characterization, and evaluation of a novel dexibuprofen-capsaicin skin emulgel with improved in vivo anti-inflammatory and analgesic effects. AAPS PharmSciTech. 2020; 21(6). [CrossRef]
[18] Ashara K C, Paun J S, Soniwala M M, Chavada J R, Mori N M.Micro-emulsion based emulgel: A novel topical drug delivery system. Asian Pac J Trop Dis. 2014; 4(1): 27-32 [CrossRef]
[19] Shelke O, Kulkarni A. Formulation, development and evaluation of nifedipine emulgel for treatment of anal fissures using polymeric emulsifiers. Indian J Pharm Educ Res. 2019; 53(2): 74-81. [CrossRef]
[20] Amasya G, Badilli U, Aksu B, Tarimci N. Quality by design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the W/O/W double emulsion – solvent evaporation method. Eur J Pharm Sci. 2016; 84: 92–102. [CrossRef]