Poj Kulvanich

Spherical composite particles of rice starch and microcrystalline cellulose: A new coprocessed excipient for direct compression

Composite particles of rice starch (RS) and microcrystalline cellulose were fabricated by spray-drying technique to be used as a directly compressible excipient. Two size fractions of microcry stalline cellulose, sieved (MCS) and jet milled (MCJ), having volumetric mean diameter (D50) of 13.61 and 40.51 μm, respectively, were used to form composite particles with RS in various mixing ratios. The composite particles produced were evaluated for their powder and compression properties. Although an increase in the microcrystalline cellulose proportion imparted greater compressibility of the composite particles, the shape of the particles was typically less spherical with rougher surface resulting in a decrease in the degree of flowability. Compressibility of composite particles made from different size fractions of microcrystalline cellulose was not different; however, using MCJ, which had a particle size range close to the size of RS (D50=13.57 μm), provided more spherical particles than using MCS. Spherical composite particles between RS and MCJ in the ratio of 7∶3 (RS-MCJ-73) were then evaluated for powder properties and compressibility in comparison with some marketed directly compressible diluents. Compressibility of RS-MCJ-73 was greater than commercial spray-dried RS (Eratab), coprocessed lactose and microcrystalline cellulose (Cellactose), and agglomerated lactose (Tablettose), but, as expected, lower than microcrystalline cellulose (Vivapur 101). Flowability index of RS-MCJ-73 appeared to be slightly lower than Eratab but higher than Vivapur 101, Cellactose, and Tablettose. Tablets of RS-MCJ-73 exhibited low friability and good self-disintegrating property. It was concluded that these developed composite particles could be introduced as a new coprocessed direct compression excipient.

Fundamental considerations in the measurement of adhesional forces between particles using the centrifuge method

The adhesional characteristics of interactive mixtures of HPMCP-coated glass spheres and several powdered drugs were investigated using a specially designed centrifuge cell. The adhesion profile of percent of drug remaining on the carrier versus the square of the speed of rotation was log normally distributed; the degree of adhesion could be characterized by the speed of rotation to detach 50% of the particles (S50) and the standard deviation of the distribution (σ). All the powders tested using this model interactive system possessed log normal adhesion profiles. The system was validated by testing the effect of the interactive mixture loadings and the time of centrifuging at each rotational speed on the adhesion profile. Loads between 60 and 150 mg, and centrifuging times of 30 and 60 s caused no significant change to the S50 value obtained for a sulphapyridine interactive mixture.

Influence of relative humidity on the adhesive properties of a model interactive system

Abstract— The influence of relative humidity on the adhesive properties of model drug‐carrier interactive systems was investigated using the centrifuge method. The degree of adhesion was quantified by determining the S50 from the adhesion profile. High ambient humidity (greater than 40% r.h.) decreased the degree of interaction of three sulphonamide powders with model hydroxypropyl methylcellulose phthalate‐coated glass bead carriers during blending. All drug‐carrier interactive systems displayed decreases in the degree of adhesion during storage. The extent and rate of the decreases increased with relative humidity and was interactive system‐dependent. Preconditioning the powders to varying moisture contents produced contrasting results during blending, with one system showing a decrease in adhesion as the relative humidity increased, while the others interactive capability increased. This increase was attributed to the enhancement of charging sites on the drugs powders surface by the adsorbed moisture.

The effect of particle size and concentration on the adhesive characteristics of a model drug‐carrier interactive system

The effect of concentration and particle size on the adhesive tendency of drug particles in a model interactive system was investigated using a centrifuge technique. The model interactive system consisted of drug powders adhered to coated glass carrier beads. Adhesion profiles of per cent of drug remaining on the carrier versus the square of the speed of rotation were a logarithmic normal function. Increase in the adherent particle size and concentration decreased the adhesive tendency of all drug powders studied. Particle collisions during detachment and the formation of multiparticulate layers even before the monolayer saturation of the carrier surface were responsible for the reduced adhesive stability of the drugs on the carrier as the particle loading increased.

Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery

Purpose The aim of the present study was to prepare inhalable co-spray dried powders of salmon calcitonin loaded chitosan nanoparticles (sCT-CS-NPs) with mannitol and investigate pulmonary absorption in rats. Methods The sCT-CS-NPs were prepared by the ionic gelation method using sodium tripolyphosphate (TPP) as a cross-linking polyion. Inhalable dry powders were obtained by co-spray drying aqueous dispersion of sCT-CS-NPs and mannitol. sCT-CS-NPs co-spray dried powders were characterized with respect to morphology, particle size, powder density, aerodynamic diameter, protein integrity, in vitro release of sCT, and aerosolization. The plasmatic sCT levels following intratracheal administration of sCT-CS-NPs spray dried powders to the rats was also determined. Results sCT-CS-NPs were able to be incorporated into mannitol forming inhalable microparticles by the spray drying process. The sCT-CS-NPs/mannitol ratios and spray drying process affected the properties of the microparticles obtained. The conformation of the secondary structures of sCTs was affected by both mannitol content and spray dry inlet temperature. The sCT-CS-NPs were recovered after reconstitution of spray dried powders in an aqueous medium. The sCT release profile from spray dried powders was similar to that from sCT-CS-NPs. In vitro inhalation parameters measured by the Andersen cascade impactor indicated sCT-CS-NPs spray dried powders having promising aerodynamic properties for deposition in the deep lung. Determination of the plasmatic sCT levels following intratracheal administration to rats revealed that the inhalable sCT-CS NPs spray dried powders provided higher protein absorption compared to native sCT powders. Conclusion The sCT-CS-NPs with mannitol based spray dried powders were prepared to have appropriate aerodynamic properties for pulmonary delivery. The developed system was able to deliver sCT via a pulmonary route into the systemic circulation.

Miscibility and interactions between 17β-estradiol and Eudragit® RS in solid dispersion

Miscibility of 17beta-estradiol and Eudragit RS in solid dispersions was determined by modulated temperature differential scanning calorimetry (MTDSC). A reduction of the 17beta-estradiol melting point in Eudragit RS solid dispersions was observed by MTDSC using heating program I in which the maximum temperature in the first heating run was lower than the 17beta-estradiol melting point. The melting point depression of 17beta-estradiol in solid dispersions as a function of composition could be explained by the Nishi-Wang equation indicating an interaction between 17beta-estradiol and Eudragit RS in the system. A variation of glass transition temperature (T(g)) of 17beta-estradiol in Eudragit RS solid dispersion was observed by MTDSC using heating program II in which the maximum temperature in the first heating run reached the 17beta-estradiol melting point. In the second heating run of heating program II, 17beta-estradiol was in an amorphous form blended with Eudragit RS. The variation in T(g) of amorphous 17beta-estradiol blended with Eudragit RS could be explained by the Kwei equation, a modified version of the Gordon-Taylor equation. The parameter estimates from the Kwei equation were consistent with an interaction between 17beta-estradiol and Eudragit RS, which was due to inter-associated hydrogen bonding as deduced from the FTIR spectra of the blends.

Influence of Incorporation Methods on Partitioning Behavior of Lipophilic Drugs into Various Phases of a Parenteral Lipid Emulsion

The purpose of this study was to investigate the effect of drug incorporation methods on the partitioning behavior of lipophilic drugs in parenteral lipid emulsions. Four lipophilic benzodiazepines, alprazolam, clonazepam, diazepam, and lorazepam, were used as model drugs. Two methods were used to incorporate drugs into an emulsion: dissolving the compound in the oil phase prior to emulsification (de novo emulsification), and directly adding a concentrated solution of drug in a solubilizer to the emulsion base (extemporaneous addition). Based on the molecular structures and determination of the oil and aqueous solubilities and the partition coefficients of the drugs, the lipophilicity was ranked as diazepam > clonazepam > lorazepam > alprazolam. Ultracentrifugation was used to separate the emulsion into four phases, the oil phase, the phospholipid-rich phase, the aqueous phase and the mesophase, and the drug content in each phase was determined. Partitioning of diazepam, which has the highest lipophilicity and oil solubility among the four drugs, was unaffected by the drug incorporation method, with both methods giving a high proportion of drug in the inner oil phase and the phospholipid-rich phase, compared to the aqueous phase and mesophase. Partitioning of the less lipophilic drugs (alprazolam, clonazepam, and lorazepam) in the phases of the emulsion system was dependent on the method of incorporation and the drug solubility properties. Emulsions of the three drugs prepared by de novo emulsification exhibited higher drug localization in the phospholipid-rich phase compared to those made by extemporaneous addition. With the latter method, the drugs tended to localize in the outer aqueous phase and mesophase, with less deposition in the phospholipid-rich phase and no partitioning into the inner oil phase.

The effect of blending time on particle adhesion in a model interactive system

The adhesive tendency of drug particles in a model drug carrier interactive system increased with blending time. The degree of interaction was measured using a centrifuge technique; the resultant adhesion profile of per cent retained on the carrier versus the square of the speed of rotation was a logarithmic normal function that allowed the determination of the S50 to characterize the adhesion tendency. The relative degree of adhesion of the drug particles in the interactive mixtures and the rate to attain adhesion saturation in the interactive system during the mixing process was markedly different for the three mixtures studied. The increased adhesive tendencies during blending were probably associated with triboelectrification of the drug and carrier particles.

Release Characteristics of the Matrices Prepared from Co-spray-Dried Powders of Theophylline and Ethylcellulose

ABSTRACT Co-spray-dried powders of theophylline and ethylcellulose were prepared using aqueous ethylcellulose dispersion. Co-spray-dried powders were directly compressed into the matrices and the release characteristics of the prepared matrices were investigated. The co-spray-dried powders exhibited good matrix formations with high hardness at rather low compression force. The concentration of ethylcellulose in the matrices was, as expected, the rate-determining factor in controlling the release rate of the drug. Increasing the weight fractions of ethylcellulose resulted in a corresponding decrease in the drug release rates in both 0.1 N HCl and phosphate buffer pH 6.8. However, at the same level of ethylcellulose content, the drug release in acidic conditions was higher than in alkaline medium. To modify release characteristics of the matrices, PVP K30 and lactose were employed as channeling agents. At concentrations of 5 and 10%, PVP K30 was found to slow the drug release when incorporated into the co-spray-dried powder formulations containing 5% ethylcellulose. Lactose at a concentration of 15% provided an increasing effect on drug release when added in the formulations. But an increase in lactose quantity from 15 to 25% did not exert much more influence on release characteristics. Higuchi plots were found to be best applicable to all release data. Scanning electron microscopic examinations on the surface and cross-section of the matrices before and after subjection to release testing revealed the formation of porous networks within the matrices by the ethylcellulose fibers. Such polymeric networks would account for the controlled diffusion of the drug from the matrices.

Correlation between total adhesion and charge decay of a model interactive system during storage

The effect of storage at 33% relative humidity on the degree of particle adhesion of model drug-carrier interactive systems was studied. A centrifuge method was used to determine total particle adhesion characterized by the S50 value while the electrostatic particular detachment charge was measured with an air stream Faraday cage. All interactive systems showed decreases in the extent of interaction during storage over 23 days with the type of drug-carrier system influencing the rate of adhesive change. Good correlation was obtained between the total adhesion and the electrostatic charge produced on particle detachment. A theoretical model was developed which allowed the estimation of the non-electrical interactive force contribution of each drug system.