The effect of mesoporous silica impregnation on tribo-electrification characteristics of flurbiprofen

Tribo-electrification is a common occurrence within the pharmaceutical industry where solid dosage forms constitute majority of pharmaceutical formulations. Tribo-electrification of powders leads to a range of complications such as adhesion of particulate material to the processing equipment resulting in segregation, affecting the content uniformity. Flurbiprofen, a highly charging material, was used as a model drug to investigate the tribo-electrification and adhesion characteristics by impregnating the model drug inside a mesoporous silica matrix. The model drug was impregnated using i) solvent loading, and ii) physical mixing methods, at varying degree of silica to drug ratio (5-20% w/w). The resulting mixtures were tribo-charged using a custom built device based on a shaking concept inside a stainless steel capsule, consisting of a Faraday cup and connected to electrometer. The electrostatic charge and the percentage adhesion of Flurbiprofen were reduced in both drug loading methods. The solvent impregnation method using acetone was more successful at reducing the electrostatic charge build up on flurbiprofen than physical powder mixing. The percentage adhesion to the shaking capsule was reduced notably as a result of loading the drug in the SBA-15 porous network. The results illustrate that the incorporation of highly charged model drug inside a low-charging pharmaceutical carrier system to be an effective approach in control the induction of tribo-electrification phenomena during powder processing

Urea Finishing Process: Prilling versus Granulation

Solid urea is the largest nitrogen fertilizer product which is produced in two forms of granules and prills. Although the chemical properties of both prills and granules remain similar, their different physical and mechanical properties are distinguishable and make them suitable for different application either as fertilizer or raw materials for chemical industry. The objective of this work is to analyses physical and mechanical properties of urea granules produced in two different plants in Malaysia using fluidized bed process and compare them with the imported urea prills to the country; hence make a process-product relationship for urea finishing processes. Results of size distribution of the samples show that the most of the granules fall in the size range between 2.40 and 3.50 mm, whereas the prills size is around 1.60 mm. Strength measurement using side crushing test also shows that the prills with the average failure load of 3.80 N remain significantly weaker than the granules with failure load of 10-17 N. Strength distribution of the particles also shows that a more uniform strength distribution is observed for the prills than the granules. It is concluded that the urea prilling process is the finishing process which produces the weaker and the more uniform size and strength of the particles than the fluidized-bed granulation process

Drug release from E chemistry hypromellose tablets using the Bio-Dis USP type III apparatus: an evaluation of the effect of systematic agitation and ionic strength

The aim of the study was to evaluate the effect of systematic agitation, increasing ionic strength and gel strength on drug release from a gel-forming matrix (HPMC E10M, E4M and E50LV) using USP type III Bio-Dis apparatus with theophylline as a model drug. The triboelectric charging; particle sizing, water content, true density and SEM of all the hypromellose grades, theophylline and formulated blends were characterised. The results showed that balanced inter-particulate forces exist between drug particles and the excipient surface and this enabled optimum charge to mass ratio to be measured. Agitation and ionic strength affected drug release from E50LV and E4M tablet matrices in comparison to the E10M tablet matrices. Drug release increased substantially when water was used as the dissolution media relative to media at pH 1.2 (containing 0.4 M NaCl). The results showed all f2 values for the E10M tablet matrices were above 50 suggesting the drug release from these tablet matrices to be similar. Rheological data also explained the different drug release behaviour with the stress required to yield/erode being 1 Pa, 150 Pa, and 320 Pa, for the E50LV, E4M and E10M respectively. The stiffness of the gel was also found to be varied from 2.5 Pa, 176.2 Pa and 408.3 Pa for the E50LV, E4M and E10M respectively. The lower G′ value can be explained by a softer gel being formed after tablet introduction into the dissolution media thereby indicating faster drug releas

The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices--the use of the USP III apparatus.

Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC) E4M and K4M were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The objectives of this study were to evaluate the effects of systematic agitation, ionic strength and pH on the release of theophylline from the gel forming hydrophilic polymeric matrices with different methoxyl substitution levels. Tribo-electric charging of hypromellose, theophylline and their formulated blends containing E4M and K4M grades has been characterised, along with quantitative observations of flow, compression behaviour and particle morphology. Agitations were studied at 5, 10, 15, 20, 25, 30 dips per minute (dpm) and also in the ascending and descending order in the dissolution vials. The ionic concentration strength of the media was also varied over a range of 0-0.4M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. To study the effect of ionic strength on the hydrophilic matrices, agitation was set at 20 dpm. The charge results on individual components imply that the positively charged particles have coupled with the negatively charged particles to form a stable ordered mixture which is believed to result in a more homogeneous and stable system. The particle shape analysis showed the HPMC K4M polymer to have a more irregular morphology and a rougher surface texture in comparison to the HPMC E4M polymer, possibly a contributory factor to the gelation process. The results showed gelation occurred quicker for the K4M tablet matrices. Drug release increased with increased agitation. This was more pronounced for the E4M tablet matrices. The ionic strength also had more of an effect on the drug release from the E4M matrices. The experiments highlighted the resilience of the K4M matrices in comparison with the E4M matrices. The results thus show that despite similar viscosities of E4M and K4M, the methoxyl substitution makes a difference to their control of drug release and as such care and consideration should be given to the choice of polymer used for extended release. The use of systematic change of agitation method and ionic strength may indicate potential fed and fasted effects on drug release from hydrophilic matrices

Triboelectrification and dissolution property enhancements of solid dispersions

The use of solid dispersion techniques to modify physicochemical properties and improve solubility and dissolution rate may result in alteration to electrostatic properties of particles. Particle triboelectrification plays an important part in powder processing, affecting end product quality due to particle deposition and powder loss. This study investigates the use of glucosamine hydrochloride (GLU) in solid dispersions with indomethacin. Solvents selected for the preparation of the dispersions were acetone, acetone–water, ethanol and ethanol–water. Solid state characterizations (DSC, FTIR and XRPD) and dissolution were conducted. Dispersions were subjected to charge using a custom built device based on a shaking concept, consisting of a Faraday cup connected to an electrometer. All dispersions improved the dissolution rate of indomethacin. Analysis showed the method of preparation of the dispersion induced polymorphic forms of the drug. Indomethacin had a high propensity for charging (−411 nC/g). GLU had a very low charge (−1 nC/g). All dispersions had low charges (−1 to 14 nC/g). Acetone as a solvent, or in combination with water, produced samples with an electronegative charge in polarity. The same approach with ethanol produced electropositive charging. The results show the selection of solvents can influence powder charge thereby improving powder handling as well as dissolution properties