China Science

The purpose of this study was to examine the suitability of polystyrene-coated (PS-coated) microcapsules of drug-resin complex for achieving prolonged release of diltiazem-HCl, a highly water-soluble drug, in simulated gastric; intestinal fluid. The drug was bound to Indion 254, a cation-exchange resin,; the resulting resinate was microencapsulated with PS using an oil-in-water emulsion-solvent evaporation method. The effect of various formulation parameters on the characteristics of the microcapsules was studied. Mean diameter; encapsulation efficiency of the microcapsules rose with an increase in the concentration of emulsion stabilizer; the coat/core ratio, while the same characteristics tended to decrease with an increase in the volume of the organic disperse phase. The desorption of drug from the uncoated resinate was quite rapid; independent of the pH of the dissolution media. On the other hand, the drug release from the microcapsules was prolonged for different periods of time depending on the formulation parameters; was also found to be independent of the pH of the dissolution media. Both the encapsulation efficiency; the retardation of drug release were found to be dependent on the uniformity of coating, which in turn was influenced by the formulation parameters. Kinetic studies revealed that the desorption of drug from the resinate obeyed the typical particle diffusion process, whereas the drug release from the microencapsulated resinate followed the diffusion-controlled model in accordance with the Higuchi equation. PS appeared to be a suitable polymer to provide prolonged release of diltiazem independent of the pH of the dissolution media.

Arindam Halder1?Biswanath Sa1Email:biswanathsa2003@yahoo.com
[1] Centre for Advanced Research in Pharmaceutical Sciences, Department of Pharmaceutical Technology, Jadavpur University, 700 032 Kolkata, India

This research was aimed to characterize microemulsion systems of isopropyl palmitate (IPP), water,; 2?1 Brij 97; 1-butanol by different experimental techniques. A pseudoternary phase diagram was constructed using water titration method. At 45% wt/wt surfactant system, microemulsions containing various ratios of water; IPP were prepared; identified by electrical conductivity, viscosity, differential scanning calorimetry (DSC), cryo-field emission scanning electron microscopy (cryo-FESEM); nuclear magnetic resonance (NMR). The results from conductivity; viscosity suggested a percolation transition from water-in-oil (water/oil) to oil-in-water (oil/water) microemulsions at 30% wt/wt water. From DSC results, the exothermic peak of water; the endothermic peak of IPP indicated that the transition of water/oil to oil/water microemulsions occurred at 30% wt/wt water. Cryo-FESEM photomicrographs revealed globular structures of microemulsions at higher than 15% wt/wt water. In addition, self-diffusion coefficients determined by NMR reflected that the diffusability of water increased at higher than 35% wt/wt water, while that of IPP was in reverse. Therefore, the results from all techniques are in good agreement; indicate that the water/oil; oil/water transition point occurred in the range of 30% to 35% wt/wt water.

Prapaporn Boonme1?Karen Krauel3?Anja Graf3?Thomas Rades3?Varaporn Buraphacheep Junyaprasert1Email:pyvbp@mahidol.ac.th
[1] Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 10400 Bangkok, Thailand ;[2] Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, 90112 Songkhla, Thailand ;[3] School of Pharmacy, University of Otago, PO Box 913, 9001 Dunedin, New Zealand

Conclusions The viscoelastic properties of the cream formulations were tested by 2 methods (ie, increased stress; increased frequency tests). The rheology experiments indicate that the formulations are stable; they show resistance to external forces, as their elastic properties are sustained whether or not the magnitude or frequency of external forces are increased. The results show that rheological properties of the formulations are affected by the proportion of the oil phase; the amount of carbomer in the aqueous phase, but the effect of monocaprin is modest. Increasing carbomer amount increases viscosity; elasticity. Increasing the oil volume fraction increased the structural stability of the creams. The formulation containing monocaprin, which yielded the most viscoelastic structure was a cream containing 10% oil phase; 0.5% carbomer (Formulation 9).

Thórunn ósk Thorgeirsdóttir1Email:tthorgeirsdottir@actavis.com?Halldór Thormar2?Thórdís Kristmundsdóttir1
[1] Faculty of Pharmacy, University of Iceland, Hagi, Hofsvallagtu 53, 107 Reykjavík, Iceland ;[2] Institute of Biology, University of Iceland, IS-107 Reykjavik, Iceland

The objective of this research was to estimate differences in heat; mass transfer between freeze dryers due to inherent design characteristics using data obtained from sublimation tests. This study also aimed to provide guidelines for convenient scale-up of the freeze-drying process. Data obtained from sublimation tests performed on laboratory-scale, pilot,; production freeze dryers were used to evaluate various heat; mass transfer parameters: nonuniformity in shelf surface temperatures, resistance of pipe, refrigeration system,; condenser. Emissivity measurements of relevant surfaces such as the chamber wall; the freeze dryer door were taken to evaluate the impact of atypical radiation heat transfer during scale-up. “Hot”; “cold” spots were identified on the shelf surface of different freeze dryers,; the impact of variation in shelf surface temperatures on the primary drying time; the product temperature during primary drying was studied. Calculations performed using emissivity measurements on different freeze dryers suggest that a front vial in the laboratory lyophilizer received 1.8 times more heat than a front vial in a manufacturing freeze dryer operating at a shelf temperature of 25°C; a chamber pressure of 150 mTorr during primary drying. Therefore, front vials in the laboratory are much more atypical than front vials in manufacturing. Steady-state heat; mass transfer equations were used to study a combination of different scaleup issues pertinent during lyophilization cycles commonly used for the freeze-drying of pharmaceuticals.

S. Rambhatla1?S. Tchessalov1?Michael J. Pikal1Email:pikal@uconnvm.uconn.edu
[1] School of Pharmacy, University of Connecticut, 06269 Storrs, CT ;[2] Present address: Talecris Biotherapeutic, Inc., Clayton, NC ;[3] Present address: Wyeth BioPharma, Drug Products Development, Andover, MA

The purpose of this study was to achieve a better therapeutic efficacy; patient compliance in the treatment for vaginitis. Clotrimazole (1%) has been formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%) together with mucoadhesive polymers such as Carbopol 934; hydroxypropylmethylcellulose (0.2% for both). To increase its aqueous solubility., clotrimazole was incorporated as its inclusion complex with 1?1 molar ratio with ?-cyclodextrin. The inclusion complex was thoroughly characterized using various techniques, including [1]H NMR spectroscopy, FT IR spectrophotometry, differential scanning calorimetry, scanning electron microscopy, phase solubility studies,; determination of stability constant (k1?1). The gelation temperature; rheological behavior of different formulations at varying temperatures were measured. In vitro release profiles of the gels were determined in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin slowed down the release of clotrimazole considerably. Carbopol 934, on the other hand, was found to interact with ?-cyclodextrin, inducing precipitation. As far as rheological properties are concerned, thermosensitive in situ gelling was obtained with formulations containing drug: cyclodextrin complex rather than with free drug. Thus, the optimum formulation for a controlled-release thermosensitive; mucoadhesive vaginal gel was determined to be clotrimazole: ?-cyclodextrin 1% with 0.2% hydroxypropylmethylcellulose in Pluronic F127 gel (20%) providing continuous; prolonged release of active material above MIC values.

Erem Bilensoy1Email:eremino@hacettepe.edu.tr?M. Abdur Rouf1?Imran Vural1?Murat ?en2?A. Atilla Hincal1
[1] Department of Pharmaceutical Technology, Hacettepe University, Faculty of Pharmacy, 06100 Ankara, Turkey ;[2] Department of Chemistry, Hacettepe University, 06532 Beytepe-Ankara, Turkey

The aim of this study was to evaluate the effect of increasing epinephrine load on the characteristics of fast-disintegrating sublingual tablets for the potential emergency treatment of anaphylaxis. Four tablet formulations, A, B, C,; D, containing 0%, 6%, 12%,; 24% of epinephrine bitartrate, respectively,; microcrystalline cellulose:low-substituted hydroxypropyl cellulose (9?1), were prepared by direct compression, at a range of compression forces. Tablet weight variation, content uniformity, hardness, disintegration time, wetting time,; friability were measured for each formulation at each compression force. All 4 tablet formulations at each compression force were within the United States Pharmacopeia (USP) limits for weight variation; content uniformity. A linear increase in compression force resulted in an exponential increase in hardness for all formulations, a linear increase in disintegration; wetting times of A,; an exponential increase in disintegration; wetting times of B, C,; D. At a mean±SD hardness of ?2.3±0.2 kg, all tablet formulations passed the USP friability test. At a mean±SD hardness of ?3.1±0.2 kg, all tablet formulations resulted in disintegration; wetting times of >10 seconds; >30 seconds, respectively. Tablets with drug loads from 0% to 24% epinephrine can be formulated with hardness, disintegration times,; wetting times suitable for sublingual administration.

Mutasem M. Rawas-Qalaji1?F. Estelle2?R. Simons2?Keith J. Simons3Email:simons@ms.umanitoba.ca
[1] Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada ;[2] Section of Allergy; Clinical Immunology, Department of Pediatrics; Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada ;[3] Faculty of Pharmacy, Department of Pediatrics; Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

Fluid dynamics of pellets processed in bottom spray traditional Wurster coating; swirl accelerated air (precision) coating were compared with the intent to understand; facilitate improvements in the coating processes. Fluid dynamics was described by pellet mass flow rate (MFR) obtained using a pellet collection system; images captured using high speed photography. Pellet flow within the partition column was found to be denser; slower in Wurster coating than in precision coating, suggesting a higher tendency of agglomeration during the coating process. The influence of partition gap; load on the MFR indicated that the mechanism of transport of pellets into the coating zone in precision coating depended on a strong suction, whereas in Wurster coating, pellets were transported by a combination of peripheral fluidization, gravity,; weak suction pressure. In precision coating, MFR was found to increase uniformly with air flow rate; atomizing pressure, whereas MFR in Wurster coating did not correlate as well with air flow rate; atomizing pressure. This demonstration showed that transport in precision coating was air dominated. In conclusion, fluid dynamics in precision coating was found to be air dominated; dependent on pressure differential, thus it is more responsive to changes in operational variables than Wurster coating.

L. W. Chan1?Elaine S. K. Tang1?Paul W. S. Heng1Email:phapaulh@nus.edu.sg
[1] Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543 Singapore

The purpose of this study was to evaluate DNA degradation upon thermal heating using dielectric relaxation; direct current (DC) conductivity methods. Herring sperm DNA, human growth hormone (HgH) plasmid DNA,; secreted alkaline phosphatase (SEAP) plasmid DNA were used as the examples. DNA was heated at 80°C for 1 hour. The dielectric relaxation spectra as a function of the applied field frequency were measured for HgH DNA at 0.5 hours; at 1 hour. The frequency range covered was from 10 kHz to 100 kHz. The DC conductivity measurements were made for all 3 kinds of DNA at 4 time points: 0 hours, 0.5 hours, 0.75 hours,; 1 hour. At each time point the DC conductivity was measured for each sample as a function of concentration via water dilution. The results show that the dielectric relaxation method is less sensitive in characterizing heat-driven DNA degradation. Conversely, DC conductivity is very sensitive. The semiquantitative dependence of the conductivity upon heating suggests that DNA degradation involves more than plasmid DNA nicking. Double strand; single strand breaks may also occur. In addition, herring sperm DNA, HgH DNA,; SEAP DNA, though similar in their DC conductivity functional forms upon dilution, exhibit significant differences in their responses to sustained heating.

Jonathan I. Sheu1?Eric Y. Sheu2Email:ericsheu@comcast.net
[1] Acalanes High School, 1200 Pleasant Hill Rd, 94549 Lafayette, CA ;[2] 7 Olde Creek Place, 94549 Lafayette, CA