Continuous production of aqueous suspensions of ultra-fine particles of curcumin using ultrasonically driven mixing device

Abstract

Developing drug formulations for poorly water-soluble drugs is a major challenge for pharmaceutical industries as the poor water solubility limits bioavailability of these drugs. Production of nanoparticles/microparticles of these drugs is one of the ways to improve dissolution rates by increasing interfacial area for dissolution. Curcumin, a compound obtained from the rhizome of curcuma longa (turmeric roots), is a pharmaceutically viable molecule. However, poor aqueous solubility limits its therapeutic use. In this work, we report studies conducted to continuously produce aqueous suspensions of curcumin nano/micro particles. Influence of process parameters such as ultrasound, additives, and solvent to antisolvent ratio on polymorphic outcome and morphology of precipitated particles has been investigated. Ultrasound was found to greatly influence the polymorphic form and the morphology of precipitated particles. Nucleation rates, mixing time, and solid–liquid interfacial energies were also estimated to understand the effect of various processing parameters on the precipitation process.     

Enhancing tablet disintegration characteristics of a highly water-soluble high-drug-loading formulation by granulation process

Abstract

The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2^(4?1) fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p?=?.0009), inlet T (p?=?.0062), atomization air pressure (p?=?.0134) and the interaction effect between inlet T*spray rate (p?=?.0241). The compactibility of the final blend was affected significantly by disintegrant amount (p?<?.0001), atomization air pressure (p?=?.0013) and spray rate (p?=?.05). It was observed that the fluid-bed batches gave significantly lower disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches.     

Absent left common carotid artery in a right aortic arch: Separate origins of left internal and external carotid arteries from brachiocephalic artery

We present a case of cyanotic congenital heart disease with left common carotid artery agenesis in the setting of the right aortic arch highlighting the potential implications in management.     

A two-vessel aortic arch: Rare configuration with bilateral brachiocephalic arteries

We present a case of type B aortic dissection with a rare aortic arch branching variation whereby two separate brachiocephalic trunks arise from the arch. This case also highlights the potential implications of this variant in the management of thoracic aortic dissections and aneurysms.     

Induction of renin activity by gonadotropic hormones in cultured Leydig tumor cells

The hormonal regulation of renin activity in cloned and cultured Leydig tumor cells (designated MA-10) was examined. The treatment of Leydig cell cultures with bovine LH (bLH), hCG, or with (Bu)2cAMP elicited a dose- and time-dependent induction of renin activity and a concomitant increase in steroid biosynthesis. The optimum concentration of hCG was 25 ng/ml, which caused an average 25-fold increase in renin activity compared to the control value. bLH action was optimum at 75-100 ng/ml and induced an approximately 35-fold increase in renin activity. The maximum inducible level of renin activity was attained after 8-9 h of hormone treatments. The addition of progesterone (the major steroid product of the MA-10 cells) did not induce a significant increase in renin activity. Treatment of MA-10 cells with epidermal growth factor also failed to produce any increase in renin activity. The optimum concentration of (Bu)2cAMP was 800 microM for the induction of renin activity and caused an approximately 40-fold increase compared to the control value. Renin activity induced by bLH, hCG, or (Bu)2cAMP was completely inhibited by mouse anti-renin antibody, indicating the specific nature of renin. Upon withdrawal of (Bu)2cAMP from the culture medium, renin activity gradually declined to the control level, and with retreatment of these cultures with (Bu)2cAMP, a newly induced state of enzyme activity was resumed. Indirectly, the role of new protein and RNA synthesis was examined during hormonal regulation of renin induction using protein and RNA synthesis inhibitors such as cycloheximide, puromycin, actinomycin D, or rifampicin. Both protein and RNA synthesis inhibitors blocked the induction of renin activity in the presence of all three inducing agents, bLH, hCG, or (Bu)2cAMP. The results provide evidence that the induction of renin activity is modulated by bLH, hCG, or (Bu)2cAMP and represent the de novo synthesis of enzyme molecules.