Effect of ethanolic extract of Quisqualis indica L. flower on experimental esophagitis in albino Wistar rats.

Quisqualis indica L., Syn. Combretum indicum (L.) DeFilipps., known as Rangoon creeper or Chinese Honeysuckle, is an abundant source of phenols and flavonoids thathave crucial role in free radical scavenging. Therefore, here we investigated whether extract of Q. indica flower has any role against esophagitis through scavenging of free radical oxygen species. In this study, we elucidated the effect of ethanolic flower extract of Q. indica on experimental esophagitis in albino Wister rats. The fasted animals divided into six groups and received carboxymethyl cellulose (CMC) (0.25%, 3 mL/kg, Sham control) or toxic control or pantoprazole (30 mg/kg) or flower extract of different doses (100, 200 and 300 mg/kg) were subjected to pylorus and fore stomach ligation. All the animals were sacrificed after 8 h and evaluated for various parameters such as total acidity, free acidity, gastric pH, volume of gastric juices and esophagitis index. Esophageal tissues were subjected to estimation of various oxidative stress parameters like malonaldehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and protein carbonyl (PC). In a separate experiment, in vitro antioxidant assays such as DPPH and H2O2 assays, total phenolic and flavonoid contents were also conducted. The results revealed that treatments with pantoprazole and flower extracts significantly inhibited the gastric secretion, total acidity and esophagitis index. Various oxidative stress parameters also restored to normal level in the treated groups. This action could be due to the presence of higher phenolic and flavonoid contents. All these findings collectively suggest that the flower extract of Q. indica possibly possess anti-esophagitis potential.

Moistening liquid-dependent de-aggregation of microcrystalline cellulose and its impact on pellet formation by extrusion-spheronization.

The wet-state particle size of microcrystalline cellulose (MCC) dispersed in different moistening liquids was characterized to elucidate the effect of moistening liquid type on the extent of MCC particle de-aggregation. Cohesive strength of moistened MCC masses was also assessed and pellet production by extrusion-spheronization attempted. MCC dispersed in alcohol or water-alcohol mixtures with higher alcohol proportions generally had larger particle sizes. Moistened mass cohesive strength decreased and poorer quality pellets were obtained when water-alcohol mixtures with higher alcohol proportions were used as the moistening liquid. MCC comprise aggregates of small sub-units held together by hydrogen bonds. As MCC particle de-aggregation involves hydrogen bond breaking, moistening liquids with lower polarity, such as water-alcohol mixtures with higher alcohol proportions, induced lesser de-aggregation and yielded MCC with larger particle sizes. When such water-alcohol mixtures were employed during extrusion-spheronization with MCC, the larger particle size of MCC and lower surface tension of the moistening liquid gave rise to moistened masses with lower cohesive strength. During pelletization, agglomerate growth by coalescence and closer packing of components by particle rearrangement would be limited. Thus, weaker, less spherical pellets with smaller size and wider size distribution were produced.

Influence of starting material particle size on pellet surface roughness.

The purpose of this study was to investigate the effect of pelletization aids, i.e., microcrystalline cellulose (MCC) and cross-linked polyvinyl pyrrolidone (XPVP), and filler, i.e., lactose, particle size on the surface roughness of pellets. Pellets were prepared from powder blends containing pelletization aid/lactose in 1:3 ratio by extrusion-spheronization. Surface roughness of pellets was assessed quantitatively and qualitatively using optical interferometry and scanning electron microscopy, respectively. Both quantitative and qualitative surface studies showed that surface roughness of pellets depended on the particle size of XPVP and lactose used in the formulation. Increase in XPVP or lactose particle size resulted in rougher pellets. Formulations containing MCC produced pellets with smoother surfaces than those containing XPVP. Furthermore, surface roughness of the resultant pellets did not appear to depend on MCC particle size. Starting material particle size was found to be a critical factor for determining the surface roughness of pellets produced by extrusion-spheronization. Smaller particles can pack well with lower peaks and valleys, resulting in pellets with smoother surfaces. Similar surface roughness of pellets containing different MCC grades could be due to the deaggregation of MCC particles into smaller subunits with more or less similar sizes during wet processing. Hence, for starting materials that deaggregate during the wet processing, pellet surface roughness is influenced by the particle size of the material upon deaggregation.

Insights into the functionality of pelletization aid in pelletization by extrusion-spheronization.

This study investigated the particle sizes of pelletization aids from the different wet processing steps of extrusion-spheronization, and their influence on rheological and pellet properties. Three commercial microcrystalline cellulose (MCC) grades, three commercial cross-linked polyvinyl pyrrolidone (X-PVP) grades and two agglomerated X-PVP grades (prepared using roller compaction from two commercial fine particle size X-PVP grades) were used as pelletization aid. The pelletization aids were analyzed for their dry state particle size, individual particle size (sonicated powder dispersion in water) and in-process particle sizes (dispersions of processed materials from the different processing steps). No remarkable particle size changes were observed with the commercial X-PVP grades under the different conditions. The two fine X-PVP grades, but not the coarse grade, produced good quality pellets. MCC and agglomerated X-PVP grades exhibited spectacularly lower individual and in-process particle sizes, and produced good quality pellets although some of them had dry state particle sizes comparable to that of the commercial coarse X-PVP grade. In-process particle sizes of pelletization aids correlated strongly with the rheological and pellet properties of the pelletization aid:lactose (1:3) binary mixtures. These results demonstrated that small in-process particle size of pelletization aid is a critical requirement for successful pelletization by extrusion-spheronization.

Importance of wet packability of component particles in pellet formation.

This work explored the importance of packability of component particles in the different wet processing steps of extrusion-spheronization and investigated different processing and formulation approaches for enhancing packing of component particles during extrusion-spheronization to produce spherical pellets with high yield and narrow size distribution. Various cross-linked polyvinyl pyrrolidone (XPVP) and lactose grades with different particle sizes were used as pelletization aid and filler in 1:3 binary powder blends. Loosely packed extrudates obtained from coarse XPVP/lactose blends possessed low cohesive strength and produced irregular shaped pellets with low yield whereas tightly packed, rigid extrudates obtained from XPVP/fine lactose grades possessed high cohesive strength and produced elongated pellets. Adjustment of spheronization tip speed to provide sufficient forces generated by the rotating frictional base plate for facilitating packing by rearrangement of component particles improved pellet quality. Double extrusion, decreasing particle size of the formulation component(s), and/or widening particle size distribution of the powder blend are approaches applicable to improve cohesiveness of moistened mass by closer packing of component particles for production of good quality pellets.

Influence of the Punch Head Design on the Physical Quality of Tablets Produced in a Rotary Press.

This study aims to investigate the influence of tablet punch head design on compaction and the resultant tablet mechanical properties. Tablets were prepared using flat-face punches with different head flat and head radius configurations, on a rotary tablet press with compression rolls of different diameters. The results showed that tablets produced using punches with head flats consistently displayed higher tensile strengths and lower capping tendencies. Exclusion of the head flat in the punch head geometry caused the compacts to undergo a state of continual deformation during the compaction cycle, possibly with increasing elasticity without the opportunity for more prolonged stress relaxation. Extension of head flat diameter produced small increments in dwell time and this could bring about significant improvements to the tablet mechanical quality. Changes to the punch head radius were found only to affect the compression profiles marginally, but this only produced insignificant differences in the tablet mechanical properties. A smaller compression roll allowed greater plastic flow during the dwell phase, but this was insufficient to effectively counteract the adverse effects due to increased strain rate during the consolidation phase, leading to deterioration of tablet mechanical quality.

Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach.

One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM) or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches.

HPMC-based gastroretentive dual working matrices coated with Ca(+2) ion crosslinked alginate-fenugreek gum gel membrane.

Novel alginate-fenugreek gum (FG) gel membrane coated hydroxypropylmethylcellulose (HPMC) based matrix tablets were developed for intragastric quetiapine fumarate (QF) delivery by combining floating and swelling mechanisms. The effects of polymer blend ratios [HPMC K4M:HPMC E15] and citric acid contents on time taken for 50% drug release (t50%, min) and drug release at 8h (Q8h, %) were studied to optimize the core tablets by 3(2) factorial design. The optimized tablets (F-O) exhibited t50% of 247.67±3.51min and Q8h of 71.11±0.32% with minimum errors in prediction. The optimized tablets were coated with Ca(+2) ions crosslinked alginate-FG gel membrane by diffusion-controlled interfacial complexation technique. The biopolymeric-coated optimized matrices exhibited superior buoyancy, preferred swelling characteristics and slower drug release rate. The drug release profiles of the QF-loaded uncoated and coated optimized matrices were best fitted in Korsmeyer-Peppas model with anomalous diffusion driven mechanism. The uncoated and coated tablets containing QF were also characterized for drug-excipients compatibility, thermal behaviour and surface morphology by FTIR, DSC and SEM analyses, respectively. Thus, the newly developed alginate-FG gel membrane coated HPMC matrices are appropriate for intragastric delivery of QF over a prolonged period of time with greater therapeutic benefits.

Phytochemistry, pharmacology, toxicology, and clinical trial of Ficus racemosa.

Ficus racemosa is an important medicinal plant, found in India, Australia, and Southeast Asia. It is popularly known as 'gular.' It reduces blood glucose concentration due to the presence of ß-sitosterol. Many active constituents that have been isolated from various parts of this plant possess useful pharmacological activities. The literature survey proposed that it has multiple pharmacological actions that include antidiabetic, antioxidant, antidiarrhoeal, anti-inflammatory, antipyretic, antifungal, antibacterial, hypolipidemic, antifilarial, and hepatoprotection. This review article elaborately describes the traditional uses, phytochemistry, pharmacology, and toxicology of this plant. We also provide useful structures of the secondary metabolites along with their nuclear magnetic resonance (NMR) data. Some clinical trial data have also been provided in this review. This review would assist researchers to gather scientific information in future.

Influence of rate of force application during compression on tablet capping.

Root cause and possible processing remediation of tablet capping were investigated using a specially designed tablet press with an air compensator installed above the precompression roll to limit compression force and allow extended dwell time in the precompression event. Using acetaminophen-starch (77.9:22.1) as a model formulation, tablets were prepared by various combinations of precompression and main compression forces, set precompression thickness, and turret speed. The rate of force application (RFA) was the main factor contributing to the tablet mechanical strength and capping. When target force above the force required for strong interparticulate bond formation, the resultant high RFA contributed to more pronounced air entrapment, uneven force distribution, and consequently, stratified densification in compact together with high viscoelastic recovery. These factors collectively had contributed to the tablet capping. As extended dwell time assisted particle rearrangement and air escape, a denser and more homogenous packing in the die could be achieved. This occurred during the extended dwell time when a low precompression force was applied, followed by application of main compression force for strong interparticulate bond formation that was the most beneficial option to solve capping problem.

Influence of disintegrants in different substrate physical form on dimensional recovery of multi-component tablet.

This study investigated the influence of different disintegrants, present in different substrate physical forms, on dimensional recovery of multi-component tablets prepared at different compression pressures. Formulations containing model drug, metformin, (10%, w/w), different disintegrants (10%, w/w), and lactose (80%, w/w) were compressed directly or after granulation using polyvinyl pyrrolidone (1%, w/w) as binder, into tablets (350 mg, 10mm diameter) at 150, 200, and 250 N/mm(2) compression pressures. Tablets were characterized for immediate dimensional recovery (IR) after ejection from the die, latent dimensional recovery (LR) over 24 h, tensile strength, and disintegration. The IR was predominantly contributed by crystalline components whereas LR was brought about by polymeric materials. With increased compression pressure, higher degree of plastic deformation of the polymeric disintegrants resulted in tablet with lower LR and higher tensile strength. Presence of polyvinyl pyrrolidone in the granules contributed considerably to plastic deformation, and the tablets produced had lower LR, higher tensile strength, and longer disintegration time. This study indicated that use of granules as the feed substrate physical form and a prudent selection of components may enable the coating of resultant tablets immediately after compression without the risk of coat damage due to LR.

Continuous processing and the applications of online tools in pharmaceutical product manufacture: developments and examples.

Continuous processing and production in pharmaceutical manufacturing has received increased attention in recent years mainly due to the industries' pressing needs for more efficient, cost-effective processes and production, as well as regulatory facilitation. To achieve optimum product quality, the traditional trial-and-error method for the optimization of different process and formulation parameters is expensive and time consuming. Real-time evaluation and the control of product quality using an online process analyzer in continuous processing can provide high-quality production with very high-throughput at low unit cost. This review focuses on continuous processing and the application of different real-time monitoring tools used in the pharmaceutical industry for continuous processing from powder to tablets.

Carboxymethyl xanthan microparticles as a carrier for protein delivery.

Xanthan gum (XG) was derivatized to sodium carboxymethyl xanthan gum (SCMXG) and then cross-linked with aluminium ions (Al(+3)) to prepare BSA-loaded microparticles (MPs) from a completely aqueous environment. The derivatized gum was characterized by various physical methods. Discrete and spherical BSA-loaded MPs were obtained from SCMXG solution, the pH of which was adjusted to 6 and 7 and the BSA entrapment efficiency was found to reach as high as 82%. The protein release in acidic dissolution medium was faster than that in alkaline dissolution medium and was accounted for the higher swelling ratio of the MPs in acidic environment. Moreover, the pH of the gum solution used to prepare the MPs also influenced the swelling and consequently protein release considerably.