Formulation and Characterization of Nanovesicular Systems for Ocular Drug Delivery
Rania Rasheed Elazrag;
Abstract
The use of conventional eye drops for drug delivery usually results in poor ocular drug bioavailability. This is because of the natural protection mechanisms built in the eye which are responsible for the rapid elimination of foreign objects as well as drugs from the eye.
An approach utilizing methazolamide (MZA) loaded spanlastics vesicular systems (SVs) were prepared and tested for their efficiency. These systems consisted of Span 60 mixed with different ratios of edge activators (EA) namely: Tween 60, Tween 80, Brij 35 and Brij 58, dispersed in mucoadhesive in-situ gelling mixture composed of gellan gum and HPMC.
The tested systems were designed to combine high corneal penetration properties due to drug entrapment in highly deformable spanlastics vesicles, as well as ease of application and prolonged eye retention being instilled as eye drops that undergo sol-gel transition after being in contact with tear fluids.
MZA loaded SVs were successfully prepared by ethanol injection method and characterized for their entrapment efficiency percentages (EE %), particle size (PS), zeta potential (ZP), measurement of elasticity, in vitro release and physical stability studies.
Factorial design was used to study the influence of variables on PS and EE % namely; EA type with four levels Tween 60, Tween 80, Brij 35 and Brij 58 and Span 60: EA ratio with three levels 90:10, 80:20 and 70:30 (w:w). The results suggested the selection of the best suitable formulae for further investigations being with suitable EE % and PS. The formulae showed elastic properties, sustained release for 8 hrs and good physical stability.
MZA-SVs mucoadhesive in-situ forming gels were prepared by dispersion of selected MZA loaded SVs in mixture of gellan gum and HPMC. Results of viscosity showed that the best HPMC concentration was 0.5 w/v %, the release rates of MZA–SVs mucoadhesive in-situ forming gel formulae were found to be more sustained when compared to MZA–SVs formulae, all the prepared formulae had significant mucoadhesive properties after addition of HPMC.
Sterilization was carried out by gamma radiation. The EE%, PS and gelation time were measured after sterilization. The results showed non significant change in the EE% and the gelation time after sterilization by one of the following doses: 5, 15 and 25 KGy. There was no significant change in PS after using 5 KGy, however, there was a significant change in PS after exposure to 15 and 25 KGy of gamma irradiation used.
In vivo intraocular pressure (IOP) lowering activity for the selected formulae was performed on albino rabbits and compared to that of MZA solution. All the tested MZA-SVs mucoadhesive in-situ forming gel formulae showed significantly lowering in IOP values. The selected formula composed of SP 60: TW 60 (90:10), 0.6 w/v % gellan gum and 0.5 w/v % HPMC lowered the intraocular pressure by - 8.2 mmHg within 3 hrs and effect lasted for 12 hrs.
An approach utilizing methazolamide (MZA) loaded spanlastics vesicular systems (SVs) were prepared and tested for their efficiency. These systems consisted of Span 60 mixed with different ratios of edge activators (EA) namely: Tween 60, Tween 80, Brij 35 and Brij 58, dispersed in mucoadhesive in-situ gelling mixture composed of gellan gum and HPMC.
The tested systems were designed to combine high corneal penetration properties due to drug entrapment in highly deformable spanlastics vesicles, as well as ease of application and prolonged eye retention being instilled as eye drops that undergo sol-gel transition after being in contact with tear fluids.
MZA loaded SVs were successfully prepared by ethanol injection method and characterized for their entrapment efficiency percentages (EE %), particle size (PS), zeta potential (ZP), measurement of elasticity, in vitro release and physical stability studies.
Factorial design was used to study the influence of variables on PS and EE % namely; EA type with four levels Tween 60, Tween 80, Brij 35 and Brij 58 and Span 60: EA ratio with three levels 90:10, 80:20 and 70:30 (w:w). The results suggested the selection of the best suitable formulae for further investigations being with suitable EE % and PS. The formulae showed elastic properties, sustained release for 8 hrs and good physical stability.
MZA-SVs mucoadhesive in-situ forming gels were prepared by dispersion of selected MZA loaded SVs in mixture of gellan gum and HPMC. Results of viscosity showed that the best HPMC concentration was 0.5 w/v %, the release rates of MZA–SVs mucoadhesive in-situ forming gel formulae were found to be more sustained when compared to MZA–SVs formulae, all the prepared formulae had significant mucoadhesive properties after addition of HPMC.
Sterilization was carried out by gamma radiation. The EE%, PS and gelation time were measured after sterilization. The results showed non significant change in the EE% and the gelation time after sterilization by one of the following doses: 5, 15 and 25 KGy. There was no significant change in PS after using 5 KGy, however, there was a significant change in PS after exposure to 15 and 25 KGy of gamma irradiation used.
In vivo intraocular pressure (IOP) lowering activity for the selected formulae was performed on albino rabbits and compared to that of MZA solution. All the tested MZA-SVs mucoadhesive in-situ forming gel formulae showed significantly lowering in IOP values. The selected formula composed of SP 60: TW 60 (90:10), 0.6 w/v % gellan gum and 0.5 w/v % HPMC lowered the intraocular pressure by - 8.2 mmHg within 3 hrs and effect lasted for 12 hrs.
Other data
| Title | Formulation and Characterization of Nanovesicular Systems for Ocular Drug Delivery | Other Titles | صياغة وتوصيف الأنظمة الحويصلية النانوية لتوصيل الدواء في العين | Authors | Rania Rasheed Elazrag | Keywords | Spanlastics; methazolamide; gellan gum; mucoadhesive, in situ gel; factorial design; intraocular pressure. | Issue Date | 2014 |
Recommend this item
Similar Items from Core Recommender Database
Items in Ain Shams Scholar are protected by copyright, with all rights reserved, unless otherwise indicated.