THE FORMATION AND CHARACTERIZATION OF CHITOSAN LIQUID CRYSTALS AS TRANSDERMAL PREPARATION CARRIER SYSTEMS

• Main Author: Agustin, Rini
• Format: Dissertations
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/52088
• Institution: Institut Teknologi Bandung

Liquid crystal is an intermediate phase between liquid and solid, therefore also called mesophase. In this phase the substance has the properties like a liquid but has the characteristics of a rigid arrangement and the orientation of molecules like crystalline solids. Nowdays, the use of liquid crystals in medicine and pharmacy has developed. Applications of liquid crystal in pharmaceuticals i.e as carriers of drugs and cosmetics, increasing in solubility of poor water-soluble drug, controling of drug release, and for drug stability. The material that can form liquid crystals is called mesogen, can be formed from surfactants, polymer or drugs. Research of liquid crystal in pharmaceutical applications mostly was performed from mesogen surfactants and lipids. However, liquid crystal from polymers as mesogen, especially hydrocolloid polymer is limited. Chitosan (CH) is the natural hydrocolloid polymer which qualify as liquid crystalforming (mesogen) and potential to be applied as transdermal gel delivery system. CH is ampiphile and anisotropic polymer so it can be self-assembly to form a liquid crystal system. However, studies that examine the formation and characteristics of liquid crystals in order to be applied in pharmaceuticals, such as drug/cosmetic carriers are still very limited. The purpose of this research is to study the formation of CH liquid crystals for pharmaceutical applications as a transdermal carrier system. Caffeine anhydrous and sodium diclofenac were used as a model of the drug. The study was begun by characterization of physicochemical properties of CH including crystal habit examination, X-ray diffraction analysis, thermal analysis with DSC (Differential Scanning Calorymetry), and determination of CH molecular weight by high presure gel permeation chromatography (HP-GPC). Screening formation of CH liquid crystal systems is carried out by using a liotropic system (with solvents). Several acids such as citric acid (CA), tartaric acid (TA), ascorbic acid (ASC), lactic acid (LA) at various concentrations (5 to 20% w/w) were used to dissolve CH to explore the impact on liquid crystals formation. CH with variations in variously concentration in the range of 5-20% w/w (2.5% interval) was dissolved in each of these solvents, homogenized with magnetic strirer at 200 ppm at room temperature for 30 minutes in a tightly closed vial and evaluated after 2 days. Evaluation of liquid crystal system was carried out by using a polarization microscope/PLM), DSC, FTIR spectroscopy, and SAXS (Small Angle x-ray Scattering). The results was expected to provide conclusions about the behavior and characteristics of a stable CH liquid crystal system which can later be expected to be applied to topical gel delivery systems that lead to the development of transdermal gel preparations. Furthermore, the trigger factors that can increase the self-assembly capability of CH to form a rigid system in the liquid/semi-solid phase are found. The trigger factors are physical (temperature and mechanical factors) and chemical factors. CH gel was made and observed with the temperature raised at 60?and cooled again. For mechanical factor, CH gel was change to a film form by using a film device maker and dry at room temperature. Sodium diclofenac and anhydrous caffeine were applied to gels and films, respectively. The gels and films were characterized by polarizing microscopy, XRD and SAXS. The influence of chemical factors was studied by modifying the CH which makes it more hydrophobic by adding fatty acids (palmitic acid/PA). Chitosan-palmitate (CHPA) was formed into a binary lyotropic system (dispersing it in acid solvents) and ternary lyotropic systems (dispersing in acid solvents and adding oil). Both of these systems were used as carriers for transdermal device with anhydrous caffeine and sodium diclofenac as drug models. Characterization of CH showed that CH is semicrystalline polymer with irregular habits. Molecular weights of CH was 145 ± 3.94 kDa with specific characteristic CH peaks 2?were 10.76° and 20.69° based on the confirmation results of FTIR, XRD, and DSC and GPC. The result of screening of CH liquid crystal formation show that it can be formed in 10 and 20% of CA, 10 and 20% of TA, 10% ASC with the final pH of the system in the range of 2.5-4.5. CH will dissolve in dilute organic acids at pH below pKa CH (pKa 6.3) and can form a gel at a lower pH. Because of increasing the CH concentration above the pH of the gel formation (c*), CH will be able to form a liquid crystal system which is indicated by the presence of birefringence on the polarizing microscope. Characterization was performed by microscope polarization to determine c* (the lowest concentration at which birefringence. For further research, CA and TA were used because the system which used CA and TA were more stable than LA and ASC. The SAXS results from CH hydrogel in CA and TA show that the hydrogel structure has not shown ordered structure, but has shown a hierarchical domain. In general, the higher the concentration of CH the more the domain of the hierarchical is formed. The radius of the domain formed in the region 1<q<4 nm -1 (high q range) is around 0.7-0.9 nm and at low q (0.1<q<1 nm -1 ) there is a domain cluster with a radius of 4-8 nm indicated at all concentrations of CH in CA and TA 10%. The research to determine the trigger factors for the structure of the CH hydrogel system, including physics and chemistry, shown that physical factors (mechanical and temperature) factors affect the stability of the drug model, especially caffeine. It refers to characterization with polarization microscopy, XRD and SAXS of hydrogels. CH gel can prevent caffeine recrystallization in aqueous carriers. The SAXS results from this system of gel and CH films still show there is no an orderly molecular arrangement (ordered structure) as shown by SAXS results even though birefringence has been seen on a polarizing microscope. Meanwhile, for chemical factors, modifying CH into more lipophilic by the addition of fatty acids (palmitic acid / PA) can produce CH that can form a lyotropic system (liquid crystal) based on the results of characterization with polarization microscopy, DSC, XRD and SAXS. The SAXS pattern shows the existence of a CHPA lyotropic system that has regularity with the lamellar structure, both binary and ternary systems. Penetration test was carried out on CH gel system, the CHPA binary system and the CHPA ternary system in order to study penetration of caffeine and sodium diclofenac from the device. Penetration studies were done through in vitro diffusion tests with Franz diffusion cells using snake skin membrane with Python Reticulus sheed snake skin. In general, penetration both of caffeine and sodium diclofenac in carriers with a liquid crystal system was better than ordinary gel of CH. Penetration of caffeine, a hydrophylic drug was better in ternary system of liquid crystals CHPA rather than in binary system. In contrast to lipophilic drug sodium diclofenac, its penetration capability is better in binary CHPA liquid.