Drug Designing: Open Access
Open Access

A design of experiment study to engineer the properties of chitosan nanoparticles as matrix to sustain drug release across orally disintegrating tablets

International Conference and Expo on Drug Discovery & Designing

August 11-13, 2015 Frankfurt, Germany

Arwa matoug-elwerfalli 1, Amr ElShaer *1

Posters-Accepted Abstracts: Drug Des

Abstract :

Background: sustained release orally disintegrating tablets (SR-ODT) are dosage form, that fully disintegrate within the oral cavity
and produce a long onset action, SR-ODT have proven their place over conventional tables, especially among pediatrics, geriatrics,
and psychiatrics and for people suffering from dysphagia.
Methods: A design of experiment (DoE) was first performed using Minitab to determine the effect of five independent variables on
three dependent responses when producing the nanoparticles using ionotopic gelation. The variables studied are (tripolyphosphate
concentration TPP, Chitosan concentration CS, acetic acid concentration, Chitosan: tripolyphosphate and stirring time) and the
responses are (particle size, surface charge and encapsulation efficiency). A formulation with optimum particle size, surface charge and
encapsulation efficiency was prepared and further coated with polyvinylpyrolidine (PVP), polyethylene glyol (PEG) and polyethylene
co-acrylic acid (PEAA). The coated nanoparticles were incorporated into ODTs tablet matrix made of lactose monohydrate and low
substituted hydroxypropyl cellulose and in vitro release studies were investigated. Promethazine (PMZ) was used as a module drug
for this study.
Results: Minitab studies revealed that the nanoparticles’ particle size is affected by most of the independent variables. For instance
increasing the concentration of TPP was associated with an increase in the particles size and this is possibly because of the stiffening
of the cross linking bonds between TPP and CS. For encapsulations efficiency, drug concentration and the ratio between CS:TPP were
the two main variables affecting the EE. The optimized nanoparticles showed particle size of 153.8±14 nm, surface charge of 31.4±0.9
mV and encapsulation efficiency of 99.7±0.06%. The DSC showed that PMZ was solubilized within chitosan nanoparticle, whereas
SEM images indicated that all the samples were spherical in shape with smooth surface and had similar size to that measured by DLS.
After coating and dispersing into the tablets’ matrices, the tablets were evaluated to determine the friability, disintegration time and
tensile strength. All tablets were at an appropriate friability (less than 1%) and had tensile strength above 2.5 N/mm2. Besides, all the
tablets managed to disintegrate within 40 seconds. The drug release profile was studied in 0.01M HCL solution. Tablets containing
PVP and PEG nanoparticles managed to sustain the drug release as less than 50% of the drug was released over 24hr. On the other
hand, non-coated and PEAA showed a faster rate of release, as for PEAA 60 % of the drug was released within the 24hr and 75% of
the drug was released from the non-coated nanoparticles.
Conclusions: based on the results provided from this study, nanoparticles could be used to sustain the drug release across ODTs.