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Design of cationic nanostructured heterolipid matrices for ocular delivery of methazolamide.

Youshia J, Kamel AO, El Shamy A, Mansour S - Int J Nanomedicine (2012)

Bottom Line: Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release.The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%.The ZP values of all formulae were positive, and greater than 30 mV.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

ABSTRACT
Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release. This study assessed the feasibility of using nanostructured lipid matrices (NLMs) for ocular delivery of methazolamide-(MZA) adopting heterolipids composed of novel mixtures of Compritol (®) and cetostearyl alcohol (CSA), and stabilized by Tween 80(®). The systems were prepared using the modified high shear homogenization followed by ultrasonication method, which avoids the use of organic solvents. A 3(2) full factorial design was constructed to study the influence of two independent variables, namely the ratio of CSA:Compritol and the concentration of Tween 80, each in three levels. The dependent variables were the entrapment efficiency percentages (EE%), mean particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In vivo intraocular pressure (IOP) lowering activity for the selected formulae was compared to that of MZA solution. The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%. The ZP values of all formulae were positive, and greater than 30 mV. The best formula, composed of 4% CSA, 2% Compritol, 0.15% stearylamine, and 2% Tween 80, with EE% of 25.62%, PS of 207.1 nm, PDI of 0.243, and ZP of 41.50 mV, showed in vitro sustained release properties for 8 hours and lowered the intraocular pressure by 8.3 mmHg within 3 hours, with this drop in pressure lasting for 12 hours.

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Main effect (A) and interaction plot (B) for EE% of MZA in NLMs.Abbreviations: CSA, cetostearyl alcohol; EE, entrapment efficiency; MZA, methazolamide; NLMs, nanostructured lipid matrices.
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f1-ijn-7-2483: Main effect (A) and interaction plot (B) for EE% of MZA in NLMs.Abbreviations: CSA, cetostearyl alcohol; EE, entrapment efficiency; MZA, methazolamide; NLMs, nanostructured lipid matrices.

Mentions: Figure 1A shows that increasing CSA concentration from 2 to 4 wt% significantly increased the mean EE% values of MZA in the prepared formulations from 15.13% to 26.98% (P < 0.001). This could be explained by CSA being a mixture of solid aliphatic alcohols consisting mainly of stearyl alcohol and cetyl alcohol – both have an alcohol group while Compritol is mainly composed of glyceryl dibehenate, which is an ester of behenic acid. The presence of the alcohol group and its lower number of carbon atoms means that CSA is relatively less hydrophobic than Compritol. MZA is a relatively hydrophilic drug with log p = −0.2, so CSA provided a good medium for its entrapment, and this entrapment increases with increasing CSA ratio. This agrees with previous results where fatty alcohols were found to be capable of creating a less ordered solid lipid matrix, leaving space for the accommodation of drug molecules.28 Moreover, fatty alcohols such as cetyl alcohol were reported to successfully entrap hydrophilic drugs such as buspirone HCl29 and Pentoxyfilline.30


Design of cationic nanostructured heterolipid matrices for ocular delivery of methazolamide.

Youshia J, Kamel AO, El Shamy A, Mansour S - Int J Nanomedicine (2012)

Main effect (A) and interaction plot (B) for EE% of MZA in NLMs.Abbreviations: CSA, cetostearyl alcohol; EE, entrapment efficiency; MZA, methazolamide; NLMs, nanostructured lipid matrices.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3367493&req=5

f1-ijn-7-2483: Main effect (A) and interaction plot (B) for EE% of MZA in NLMs.Abbreviations: CSA, cetostearyl alcohol; EE, entrapment efficiency; MZA, methazolamide; NLMs, nanostructured lipid matrices.
Mentions: Figure 1A shows that increasing CSA concentration from 2 to 4 wt% significantly increased the mean EE% values of MZA in the prepared formulations from 15.13% to 26.98% (P < 0.001). This could be explained by CSA being a mixture of solid aliphatic alcohols consisting mainly of stearyl alcohol and cetyl alcohol – both have an alcohol group while Compritol is mainly composed of glyceryl dibehenate, which is an ester of behenic acid. The presence of the alcohol group and its lower number of carbon atoms means that CSA is relatively less hydrophobic than Compritol. MZA is a relatively hydrophilic drug with log p = −0.2, so CSA provided a good medium for its entrapment, and this entrapment increases with increasing CSA ratio. This agrees with previous results where fatty alcohols were found to be capable of creating a less ordered solid lipid matrix, leaving space for the accommodation of drug molecules.28 Moreover, fatty alcohols such as cetyl alcohol were reported to successfully entrap hydrophilic drugs such as buspirone HCl29 and Pentoxyfilline.30

Bottom Line: Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release.The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%.The ZP values of all formulae were positive, and greater than 30 mV.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

ABSTRACT
Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release. This study assessed the feasibility of using nanostructured lipid matrices (NLMs) for ocular delivery of methazolamide-(MZA) adopting heterolipids composed of novel mixtures of Compritol (®) and cetostearyl alcohol (CSA), and stabilized by Tween 80(®). The systems were prepared using the modified high shear homogenization followed by ultrasonication method, which avoids the use of organic solvents. A 3(2) full factorial design was constructed to study the influence of two independent variables, namely the ratio of CSA:Compritol and the concentration of Tween 80, each in three levels. The dependent variables were the entrapment efficiency percentages (EE%), mean particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In vivo intraocular pressure (IOP) lowering activity for the selected formulae was compared to that of MZA solution. The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%. The ZP values of all formulae were positive, and greater than 30 mV. The best formula, composed of 4% CSA, 2% Compritol, 0.15% stearylamine, and 2% Tween 80, with EE% of 25.62%, PS of 207.1 nm, PDI of 0.243, and ZP of 41.50 mV, showed in vitro sustained release properties for 8 hours and lowered the intraocular pressure by 8.3 mmHg within 3 hours, with this drop in pressure lasting for 12 hours.

Show MeSH
Related in: MedlinePlus