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Manidipine (MDP) is generally used clinically as an antihypertensive agent; however, the bioavailability of orally administered MDP is limited due to their very low water solubility.The objectives of this research were, therefore, to increase the solubility of MDP by the formation of ternary solid dispersions (tSD) with polyethylene glycol 4000 (PEG4000) and copovidone and to improve their stability.Solid ternary phase diagram was constructed to find homogeneous solid dispersion region after melting and solidifying at low temperature with different quenching substances. The pulverized powder of solid dispersions was then determined, for their physicochemical properties, by differential scanning calorimetry, powder X-ray diffractometry, Fourier transform infrared (FTIR) spectroscopy and hot stage microscopy. The solubility and dissolution of MDP from the tSD were investigated. The physical stability of tSD was also determined under accelerated condition at 40 °C/75% relative humidity (RH) for 6 months.The results showed that MDP was molecularly dispersed in PEG4000 and copovidone when the tSD was created from homogeneous region of solid ternary phase diagram. FTIR results confirmed that strong hydrogen bonding was presented between MDP and copovidone, leading to a significant increase in the solubility and dissolution of MDP. After storage at accelerated condition (40 °C/75%RH) for 6 months, the tSD still showed a good appearance and high solubility.The results of this study suggest that tSD prepared by melting has promising potential for oral administration and may be an efficacious approach for improving the therapeutic potential of MDP.

The potential of using two natural polymers (chitosan and shellac) for the formation of nanoparticles by the process of ionic cross-linking to encapsulate bovine serum albumin, a model protein was investigated. Depending on the concentrations of chitosan, shellac and bovine serum albumin, three physical states - nanoparticle, aggregation, and solution could be observed as a result of the electrostatic force. The formation of nanoparticles was due to the balance between the repulsion force and attractive force while the imbalance between both forces resulted in the formation of aggregation and solution. The Fourier transform infrared spectroscopy and differential scanning calorimetry were applied to prove the nanoparticle formation. The particle size was characterized by the light scattering technique and was found in the range between 100 and 300 nm. The morphology of the particles, detected by transmission electron microscopy was spherical shape. The result showed that the zeta potential of the nanoparticles possessed positive charges. The concentrations of chitosan, shellac and bovine serum albumin had an influence on the physicochemical properties of the nanoparticles such as the particle size, the zeta potential, the encapsulation, the loading efficiencies and the cumulative release. Therefore, chitosan and shellac could be used to form nanoparticles for protein delivery by the ionic cross-linking method.

The objective of this study was to investigate the potential of chitosan salts as a carrier in the preparation of protein-loaded nanoparticles. Glutamic and aspartic acids were used to prepare chitosan salts of 35, 100, and 800 KDa. Nanoparticles of chitosan base, chitosan glutamate, and chitosan aspartate were produced by ionotropic gelation with sodium tripolyphosphate (TPP). Bovine serum albumin (BSA) was applied as a model protein at loading concentrations ranging from 0.2 to 2 mg/mL. The size of the nanoparticles, as measured by photon correlation spectroscopy, was in the range of 195 to 3450 nm, depending on type and molecular weight of chitosan. Nanoparticles prepared with higher molecular weight chitosan showed larger sizes. The encapsulation was controlled by the competition of BSA in forming ionic cross-linking with chitosan and by the entrapment of BSA during the gelation process. Higher BSA encapsulation efficiency (EE) was obtained for nanoparticles prepared with chitosan salts compared to those prepared with the base. The higher EE was a result of a higher degree of ionization, causing more active sites to interact with BSA. In addition, a higher and faster release of BSA from the nanoparticles into pH 7.4 buffer medium was observed for nanoparticles of the chitosan salts than was observed for nanoparticles of the chitosan base. The higher and faster release was attributed to higher EE and lower entrapment of BSA within the matrix of the nanoparticle during the gelation process. The influence of molecular weight on the property of nanoparticles exhibited different effects. The difference was a result of different organic acids used to prepare nanoparticles leading to the difference in polymer conformation and viscosity of organic acid solution. Therefore, this study showed that the characteristics of chitosan nanoparticles loaded with a protein drug could be readily modulated by changing the salt form or the molecular weight of the chitosan carrier.

The objective of this study was to investigate the effect of alkali treatment on properties of shellac. The native shellac was treated with sodium hydroxide for 15, 30, and 60 min to obtain hydrolyzed shellac. All types of shellac, namely native and hydrolyzed shellac at various times of treatment, were then prepared in films as free acid and ammonium salt forms by using ethanol and ammonium hydroxide solution, respectively. The results showed that alkali treatment caused an increase in acid value and a decrease in ester value. This is due to higher free carboxylic and hydroxyl groups caused by ester bond breaking. The longer the alkali treatment the higher impact of bond breaking, therefore, causing an increase in acid value, solubility at pH 7, strain, a decrease in ester value, water vapor permeability coefficient, and stress. The films were then kept at 40 degrees C, 75% RH for a period of three months. The aging effect led to an esterification of free carboxylic and hydroxyl groups, resulting in the significant change of acid value, ester value, and insoluble solid for both native and hydrolyzed shellac films in acid form. On the other hand, all types of shellac films in ammonium salt form exhibited a reasonable stability in physicochemical and mechanical properties as all films were protected from the esterification due to the formation of ammonium salt at the carboxylic binding site. It could be concluded that alkali treatment could produce hydrolyzed shellac with higher solubility in the intestine, the stability was yet in dilemma unless the shellac was in an ammonium salt form. The result obtained could, thus, provide a guideline in the use of shellac.