Applying the taguchi method to optimize sumatriptan succinate niosomes as drug carriers for skin delivery

• Published in: Journal of pharmaceutical sciences Vol. 101; no. 10; pp. 3845 - 3863
• Main Authors: González‐rodríguez, Maria Luisa, Mouram, Imane, Cózar‐bernal, Ma Jose, Villasmil, Sheila, Rabasco, Antonio M.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.10.2012; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: Administration, Cutaneous; Biological and medical sciences; cationic lipids; Chemistry, Pharmaceutical - methods; Cholesterol - administration & dosage; Cholesterol - chemistry; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Delivery Systems - methods; Drug Stability; extrusion; factorial design; General pharmacology; HPLC (high‐performance/pressure liquid chromatography); light scattering (dynamic); liposomes; Liposomes - administration & dosage; Liposomes - chemistry; Medical sciences; Particle Size; permeation enhancers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Signal-To-Noise Ratio; skin; Skin - metabolism; Solubility; Sumatriptan - administration & dosage; Sumatriptan - chemistry; Surface-Active Agents - administration & dosage; Surface-Active Agents - chemistry; surfactants; transdermal drug delivery; surfactants; liposomes; cationic lipids; transdermal drug delivery; extrusion; skin; factorial design; light scattering (dynamic); HPLC (high‐performance/pressure liquid chromatography); permeation enhancers; Performance evaluation; Agonist; Sumatriptan; HPLC chromatography; Lipids; Drug carrier; 5-HT1 Serotonine receptor; Serotonin agonist; Surfactant; Niosome; HPLC (high-performance/pressure liquid chromatography); Percutaneous route; Triptan derivatives; Taguchi method; Pharmaceutical technology; Antimigrainous agent; Light scattering; Liposome; Liquid chromatography; High pressure; Extrusion; Cations; Skin; Absorption enhancer; Performance; Factorial design
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23252

Niosomes formulated from different nonionic surfactants (Span® 60, Brij® 72, Span® 80, or Eumulgin® B 2) with cholesterol (CH) molar ratios of 3:1 or 4:1 with respect to surfactant were prepared with different sumatriptan amount (10 and 15 mg) and stearylamine (SA). Thin‐film hydration method was employed to produce the vesicles, and the time lapsed to hydrate the lipid film (1 or 24 h) was introduced as variable. These factors were selected as variables and their levels were introduced into two L18 orthogonal arrays. The aim was to optimize the manufacturing conditions by applying Taguchi methodology. Response variables were vesicle size, zeta potential (Z), and drug entrapment. From Taguchi analysis, drug concentration and the time until the hydration were the most influencing parameters on size, being the niosomes made with Span® 80 the smallest vesicles. The presence of SA into the vesicles had a relevant influence on Z values. All the factors except the surfactant–CH ratio had an influence on the encapsulation. Formulations were optimized by applying the marginal means methodology. Results obtained showed a good correlation between mean and signal‐to‐noise ratio parameters, indicating the feasibility of the robust methodology to optimize this formulation. Also, the extrusion process exerted a positive influence on the drug entrapment. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3845–3863, 2012