الفهرس 
AbstractOnly 14 pages are availabe for public view
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Abstract
Delivery of antipsychotic drugs using nanoparticles offers several advantages over free drug such as: The potential to increase therapeutic efficacy and decrease systemic toxicity. The capacity for prolonged drug release, allowing less-frequent administrations. The feasibility of incorporation lipophilic and hydrophilic drugs.
Improved physical stability of entrapped drugs.
The lower costs compared to liposomes drug delivery.
The ease of scale-up and manufacturing.
The formulation and process variables were optimized to obtain
nano -sized particles with maximum drug entrapment efficiency (EE) and
drug loading (DL). The equilibrium solubility and partition coefficient of
Sulpiride in different lipids and the influence of different pH conditions on
the drug solubility were also determined at 25°C.
Four methods were used to prepare SLNs namely; high shear hot
homogenization, solvent diffusion, film homogenization and cold
homogenization methods. Also, different preparation variables as
homogenization speed (HS), homogenization time (HT) and sonication
time (ST) were studied to obtain smaller particles of higher drug EE.
Moreover, the effect of changing the drug concentration, surfactant
concentration, surfactant type, soy lecithin concentration and lipid
concentration on the SLNs particle size, drug EE, DL, the yield and the
release of the drug was demonstrated.Results revealed that
1-SLNs drug loading depends upon several factors such as the type of lipid
used, solubility of the drug in lipid matrix, processing method and
concentration of surfactant.
2-Film homogenization produced higher entrapment efficiency and lower
release than other methods carried at hot condition. However, cold
homogenization method yielded SLNs with higher entrapment efficiency
and particles outside nanometer range.
3-The effect of homogenization speed and time was also observed to have a
pronounced effect on particle size. Increasing homogenization speed from
5,000 to 15,000 decreased particle size. Also, homogenization at 15,000 for
3 min was sufficient to produce smaller SLNs than that produced at higher
speed (20,000 rpm) or longer homogenization time (10 min).
Homogenization for 3 min and 10 min sonication time (ST) were found to
be optimal for the production of SLNs and further increase in HT or ST
resulted in aggregation of SLNs. It was found that the sonication step is
important for size reduction that SLNs sonicated for longer time (10 min)
showed smaller size than that sonicated for 1 min.
4- The particle size of SLNs was evaluated as function of surfactant type
and the size was arranged in the following descending order: PVA< Brij -
78< P407< P188<T40 <T80 <T20.
5-T80 and P188 resulted in the highest EE and DL and might be regarded
as non-solubilizing surfactant for Sulpiride according to solubility study.
6-The effect of surfactant concentration was studied using T80 or P188 at
different concentrations. Increasing the surfactant concentration till certain
limit resulted in smaller size of SLNs and higher release rate. T80
concentration above 2% or P188 above 2.5% decreased EE and did not
result in further size reduction.7-Soy lecithin concentration (0.5%-2%) was also studied to evaluate its
effect on physicochemical properties of prepared SLNs. The study revealed
that SLNs prepared using surfactant mixtures showed smaller size and
higher EE than that prepared with single surfactant. The smallest size,
highest EE and lowest burst release were obtained at 2% soy lecithin.
8-Different lipid concentrations were selected to prepare SLNs ranged from
1-10%w/w. It was found that upon increased lipid concentration, increasing
in particle size and EE was appeared significantly while higher lipid
concentration prolonged the drug release as more drug is encapsulated
within the lipid matrix.
9- Partition coefficient (PC) and drug solubility in lipid affected EE and
drug release. EE was arranged as SA>PA>TP while release was arranged
as TP>PA>SA. The highest PC and drug solubility in different lipid were
obtained in SA followed by PA and finally TP.