Development of a topical niosomal preparation of acetazolamide: preparation and evaluation

Abstract

Orally administered acetazolamide has a limited use in glaucoma due to the systemic side effects associated with its use. No topical formulation of acetazolamide is available, mainly because of it having a limited aqueous solubility and poor corneal permeation. To enhance the bioavailability of acetazolamide by the topical route and to improve the corneal permeability of the drug, niosomes of acetazolamide were prepared (employing span 60 and cholesterol) by different methods. Transmission electron microscopy (TEM) of the selected formulation was carried out to study the morphology. Niosomes were also prepared in the presence of dicetyl phosphate and stearylamine to obtain negatively and positively charged vesicles, respectively. It was found that the reverse-phase evaporation method (REV) gave the maximum drug entrapment efficiency (43.75%) as compared with ether injection (39.62%) and film hydration (31.43%) techniques. Drug entrapment efficiency varied with the charge and the percent entrapment efficiency for the REV method was 43.75, 51.23 and 36.26% for neutral, positively charged and negatively charged niosomes, respectively. Corneal permeability studies, however, showed that the percent permeation and the apparent permeability coefficient for the charged niosomes were less than for the neutral ones. A bioadhesive niosomal formulation of acetazolamide was also prepared and compared with the positively charged formulation, considering that both of them would have a prolonged stay in the cul-de-sac because of their expected interactions with mucin. The formulations were also compared based on their intraocular pressure (IOP)-lowering capacity. The positively charged niosomes (REV2), although showing good corneal permeability and pharmacodynamics, were however found to be inappropriate in terms of the corneal cell toxicity. The bioadhesive coated formulation (REV1bio) compared well with REV2 and also showed a much lesser toxicity. Further, the IOP-lowering effect of the developed formulations was compared with that of a marketed formulation of dorzolamide 2%, a topical carbonic anhydrase inhibitor. The developed niosomal formulations of acetazolamide showed a comparable physiological effect (33% reduction of IOP in REV1bio and 37% reduction in dorzolamide) with a duration of up to 6 h (the duration being 3 h for dorzolamide). Results of the study indicate that it is possible to develop a safe (as indicated by corneal toxicity studies) and physiologically active topical niosomal formulation of acetazolamide relative in efficiency to the newer local carbonic anhydrase inhibitor, dorzolamide. The developed formulations can form a cost effective treatment plan, which is especially important in the treatment of glaucoma, a chronic ailment affecting middle-aged to old patients.

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

“…Span Õ 60 containing vesicles had a significantly higher particle size compared on those containing Span Õ 80 (Figure 1c). According to the literature, increasing the HLB value of the surfactant monomers (decrease lipophilicity) leads to the formation of larger vesicles owing to the increase in surface free energy (Aggarwal et al, 2004;Abdelkader et al, 2010). Span Õ 60 has higher HLB (4.7) compared to Span Õ 80 (4.3) (Lingan et al, 2011).…”

Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations

“…Niosomes have been evaluated as ocular vehicles for a wide range of therapeutic classes such as anticholinergic (cyclopentolate), anti-glaucoa (acetazolamide and timolol maleate) and antibiotics (gentamicin) (Saettone et al, 1996;Vyas et al, 1998;Aggarwal et al, 2004;Abdelbary & El-gendy, 2008). Tween 20-based niosomes significantly improved the ocular bioavailability of cyclopentolate, with respect to the reference buffer drug solution and micellar solution, suggesting that it can be used as an efficient vehicle for ocular drug delivery (Saettone et al, 1996).…”

Potential Use of Niosomal Hydrogel as an Ocular Delivery System for Atenolol

“…15) Mucoadhesive polymers when used in combination with vesicular systems provide vesicles with the necessary site adherence and site retention to achieve carrier and drug targeting in topical ocular therapy and endow them with the ability to be mucoadhesive. 58,44) Carbopols is an important class of ocular bioadhesives. 79) Due to the low viscosity of colloidal suspensions of vesicles that does not allow sufficient retention time of the dosage form in the eye upon instillation, different hydrogel matrices such as carbopol have been used to increase the viscosity of topical preparation and to increase the retention time of the formulation at the site of administration due to good bioadhesive properties.…”