Limits...
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.

Show MeSH

Related in: MedlinePlus

DSC thermograms for (A) pure MZA, (B) physical mixture, (C) unloaded NLM-9, and (D) MZA-loaded formula NLM-9.Note: The arrow indicates the MZA peak at 201.10°C in the physical mixture.Abbreviations: DSC, differential scanning calorimetry; MZA, methazolamide; NLM, nanostructured lipid matrix.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3367493&req=5

f7-ijn-7-2483: DSC thermograms for (A) pure MZA, (B) physical mixture, (C) unloaded NLM-9, and (D) MZA-loaded formula NLM-9.Note: The arrow indicates the MZA peak at 201.10°C in the physical mixture.Abbreviations: DSC, differential scanning calorimetry; MZA, methazolamide; NLM, nanostructured lipid matrix.

Mentions: Figure 7 shows differential scanning calorimetry (DSC) thermograms for MZA, the physical mixture composed of Compritol, CSA, MZA, and stearylamine, unloaded NLMs, and MZA-loaded NLM formula NLM-9. Formula NLM-9 was chosen for DSC study as it showed high EE% and very small PS. MZA showed a sharp, narrow peak at 205.67°C with enthalpy of 13.18 J/g representing its melting point and confirming its crystalline nature. While the physical mixture showed a sharp narrow peak at 48.94°C with enthalpy of 14.46 J/g, this is the average of melting points of Compritol and CSA, indicating that both Compritol and CSA are found in a crystalline state. It also showed another very small peak at 201.10°C (shown by the arrow in Figure 7) with enthalpy of 0.09 J/g representing the MZA peak. The small magnitude of this peak may be due to the small amount of MZA found in the physical mixture. Both unloaded and loaded NLM-9 formulae gave rise to a broad very small peak at 51.2°C with enthalpy of 3.36 J/g and 52.95°C with enthalpy 3.10 J/g, respectively. The broadening of the peak accompanied with a decrease in the enthalpy and height of the melting peak indicates a decrease in the crystallinity of the lipids, which shows that incorporating lipids in NLMs led to major defects in the crystal lattice of the lipids, giving rise to more space to successfully entrap the drug. The onset of the peak of MZA-loaded NLM formula NLM-9 was at 47.67°C, which confirms the solid nature of lipids when exposed to body temperature (as this is above 40°C, so avoiding the presence of the nanoemulsion in which the advantages of NLMs will be lost). The disappearance of the MZA melting peak in the DSC thermogram of NLM-9 indicates that the drug is not in a crystalline state (ie, is amorphous) or molecularly dispersed in the lipid matrix. Similar results have been observed by many authors.35,37–39


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

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

DSC thermograms for (A) pure MZA, (B) physical mixture, (C) unloaded NLM-9, and (D) MZA-loaded formula NLM-9.Note: The arrow indicates the MZA peak at 201.10°C in the physical mixture.Abbreviations: DSC, differential scanning calorimetry; MZA, methazolamide; NLM, nanostructured lipid matrix.
© Copyright Policy
Related In: Results  -  Collection

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

f7-ijn-7-2483: DSC thermograms for (A) pure MZA, (B) physical mixture, (C) unloaded NLM-9, and (D) MZA-loaded formula NLM-9.Note: The arrow indicates the MZA peak at 201.10°C in the physical mixture.Abbreviations: DSC, differential scanning calorimetry; MZA, methazolamide; NLM, nanostructured lipid matrix.
Mentions: Figure 7 shows differential scanning calorimetry (DSC) thermograms for MZA, the physical mixture composed of Compritol, CSA, MZA, and stearylamine, unloaded NLMs, and MZA-loaded NLM formula NLM-9. Formula NLM-9 was chosen for DSC study as it showed high EE% and very small PS. MZA showed a sharp, narrow peak at 205.67°C with enthalpy of 13.18 J/g representing its melting point and confirming its crystalline nature. While the physical mixture showed a sharp narrow peak at 48.94°C with enthalpy of 14.46 J/g, this is the average of melting points of Compritol and CSA, indicating that both Compritol and CSA are found in a crystalline state. It also showed another very small peak at 201.10°C (shown by the arrow in Figure 7) with enthalpy of 0.09 J/g representing the MZA peak. The small magnitude of this peak may be due to the small amount of MZA found in the physical mixture. Both unloaded and loaded NLM-9 formulae gave rise to a broad very small peak at 51.2°C with enthalpy of 3.36 J/g and 52.95°C with enthalpy 3.10 J/g, respectively. The broadening of the peak accompanied with a decrease in the enthalpy and height of the melting peak indicates a decrease in the crystallinity of the lipids, which shows that incorporating lipids in NLMs led to major defects in the crystal lattice of the lipids, giving rise to more space to successfully entrap the drug. The onset of the peak of MZA-loaded NLM formula NLM-9 was at 47.67°C, which confirms the solid nature of lipids when exposed to body temperature (as this is above 40°C, so avoiding the presence of the nanoemulsion in which the advantages of NLMs will be lost). The disappearance of the MZA melting peak in the DSC thermogram of NLM-9 indicates that the drug is not in a crystalline state (ie, is amorphous) or molecularly dispersed in the lipid matrix. Similar results have been observed by many authors.35,37–39

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