Influence of processing methods on physico-mechanical properties of Ibuprofen/HPC-SSL formulation

Abstract

The objective of the present study was to investigate the influence of processing methods on the physical and mechanical properties of formulations containing Ibuprofen and HPC-SSL. The powder blends, containing Ibuprofen and HPC-SSL in ratio of 9:0.5, were processed using melt granulation (MG) by hot melt extrusion (HME) and wet granulation (WG) by high shear mixer. Formulated granules and powder blends were compressed into round flat faced tablets using Riva Piccola tablet press. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) studies proved that granulation process did not significantly alter the crystallinity of Ibuprofen, however, particle density and flow properties were significantly improved. Scanning electron microscopy (SEM) and particle size analysis corroborate with the findings that the flow characteristics of granules from MG were relatively superior to other formulations. Formulations were investigated for out-of-die compaction behaviour using Heckel, Kawakita, and CTC profile analysis. Detailed examination revealed that all three formulations differed in particle size due to the granulation, thus conferring to different compaction behaviour. In WG and MG, granulation offered an increase in particle size resulting in high compressibility along with deformation at low compression pressure. This results into low yield pressure, low yield strength, and higher densification, as compared with dry blend. The current work provides an insight into factors affecting physical and mechanical properties tablets, which can facilitate the rational selection of suitable change in processing method instead of changing excipients.     

Inhibition of agonist-induced down-regulation of the delta-opioid receptor with a proteasome inhibitor attenuates opioid tolerance in human embryonic kidney 293 cells

This study was designed to test the hypothesis that inhibition of agonist-induced delta-receptor down-regulation would block the development of opioid tolerance in a cell-based model. A human embryonic kidney 293 cell line was established that expressed an epitope-tagged delta-opioid receptor (DOR). Treatment of DOR cells with Tyr-d-Ala-Gly-Phe-d-Leu-enkephalin (DADL) resulted in a time-dependent decrease in the B(max) of delta-opioid receptor binding sites and immunoreactive receptor protein. When cells were coincubated with the proteasome inhibitor N-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal (ZLLL) and DADL, the magnitude of the agonist-induced decrease in B(max) and immunoreactive receptor protein was reduced compared with DADL treatment alone. Acute treatment of DOR cells with DADL caused a 3-fold increase in the level of phosphorylated mitogen-activated protein (MAP) kinase. Prior exposure of DOR cells to DADL completely abrogated the agonist-induced activation of MAP kinase. When DOR cells were coincubated with DADL and ZLLL, the proteasome inhibitor prevented the loss of agonist activation of MAP kinase. Acute treatment of DOR cell membranes with DADL stimulated [(35)S]guanosine 5'-3-O-(thio-)triphosphate (GTPgammaS) binding. When DOR cells were preincubated with DADL, the agonist-induced increase in [(35)S]GTPgammaS binding was attenuated. Coincubation of ZLLL and agonist partially prevented the decreased responsiveness to agonist stimulation. The results of this study demonstrated that inhibition of agonist-induced down regulation with a proteasome inhibitor attenuated opioid tolerance in a cellular model, and suggest that coadministration of a proteasome inhibitor with chronic opioid agonist treatment may be useful for limiting opioid tolerance in vivo.     

Navigating the impact of COVID‐19 on palliative care for head and neck cancer

Health care services are being confronted by a daily dilemma of who can receive critical care and who cannot. In a palliative care clinic, this apprehension gets exemplified, as these patients have limited life expectancy. The head and neck region further makes things critical, as it comprises of all the sites through which the SARS‐CoV‐2 can be transmitted. This document strives to define the ways in which the head and neck cancer services can contribute to better patient care in a triage context. Practical steps suggested are protective equipment use, ensuring access to critical drugs (such as opioids), greater use of telemedicine consultations, discussing advance care plans, and embracing the role of a wider community support.     

Evaluation of serum ferritin in screening for iron deficiency in tuberculosis

Serum ferritin (SF) values 10 µg/l are diagnostic of absent Bone Marrow Iron (BMI) stores and therefore of iron deficiency (ID). However, SF, which may be elevated as a part of acute phase reaction, is an unreliable indicator of BMI stores in the setting of chronic disorders, making it difficult to diagnose ID in these patients. Thus, in chronic disorders (CD) such as tuberculosis, bone marrow examination is the only reliable way to establish ID. This study was done in order to identify levels of SF that would be indicative of absent BMI stores and also to study a combination of hematological and biochemical parameters that would be helpful in raising the predictive power of SF in patients of tuberculosis. Fifty-five tuberculosis patients were studied and classified into Iron Deplete (ID) and Iron Replete (IR) based on BMI. Raising the cut-off values of SF from 10 µg/l to 30 µg/l diagnosed 88% of ID cases correctly, as compared with 61% when cut-off levels of 10 µg/l were used. At cut-off values higher than 30 µg/l, the sensitivity was markedly reduced. Therefore, raising cut-off levels of SF to 30 µg/l was most effective in predicting absent BMI, especially in a population where ID is highly prevalent. Combination of SF 30 µg/l with mean corpuscular volume (MCV), erythrocyte sedimentation rate (ESR) and total iron binding capacity (TIBC) did not improve the predictive power of SF further. Also, 89.5% cases could be correctly classified by logistic regression equations using SF with ESR and C- reactive protein (CRP).Abbreviations SF Serum ferritin - BMI Bone marrow iron - ID Iron deplete - IR Iron replete - CD Chronic disorders - MCV Mean corpuscular volume - TIBC Total iron binding capacity - ESR Erythrocyte sedimentation rate - ACD Anemia of chronic disorders - IDA Iron deficiency anemia - Hb Hemoglobin concentration - TLC Total leukocyte count - RBC Red blood cell - RDW Red cell distribution width - % TS Percent transferrin saturation - SI Serum iron     

Birth weight, childhood growth and abdominal obesity in adult life.

OBJECTIVE: To examine the relationship of adult abdominal obesity to birth weight, childhood growth and lifetime socioeconomic circumstances. METHODS: A cohort of 3200 men and women with measured waist and hip circumference, height and weight at age 43 who have been followed since their birth in March 1946 in England, Scotland and Wales. Regression models were used to examine mean waist-hip ratio and waist circumference in relation to prospective measures of birth weight, weight relative to height in childhood at ages 4, 7, 11 and 15 and adult body mass index, and to test the independent and interactive nature of the associations and adjust for childhood and adult social class. RESULTS: There was a small inverse effect of birth weight on waist-hip ratio (P=0.037) but not waist circumference in women, after adjustment for current body size. Relative weight at age 7 was inversely related to waist-hip ratio and waist circumference in men (P<0.001 for both) and waist circumference in women (P=0.007) after adjustment for current body size. These relationships were attenuated in men of large body mass index (P<0.01 for interactions between relative weight at 7 y and body mass index in both cases) but were not modified by birth weight. Relative weights at other ages showed similar patterns to those observed at age 7, the effect being weakest at age 4. These findings were independent of lifetime socioeconomic circumstances. CONCLUSION: This study found a small prenatal inverse effect of fetal growth on adult waist-hip ratio due to a reduced hip size. There was also an inverse postnatal effect of childhood growth such that for any given adult body size those who had been lighter in childhood were more at risk of abdominal obesity. These relationships were independent of childhood socioeconomic circumstances and support the idea that insulin resistance may be linked to low weight in childhood.     

Ultrapure alginate anti-adhesion gel does not impair colon anastomotic strength

Background

Ultrapure alginate gel is promising in terms of adhesion prevention. Because anti-adhesive barriers have been shown to disturb healing of bowel anastomoses, the effect of ultrapure alginate gel on the repair of colon anastomoses was studied.

Materials and methods

In 102 male Wistar rats, a 0.5-cm segment was resected from the descending colon and continuity was restored by an inverted single-layer end-to-end anastomosis. Animals were randomized into a control, an alginate gel, and a sodium hyaluronate carboxymethyl cellulose film group, each n = 34. Half of each group was sacrificed at day 3 and 7 postoperatively. Anastomotic strength was assessed by measuring both bursting pressure and breaking strength. Hydroxyproline content was measured and histologic analysis was performed. The incidence of adhesion and abscess formation was scored at sacrifice.

Results

No difference in either anastomotic-bursting pressure or breaking strength was found between experimental groups and the controls at any time point. Both the incidence of adhesion formation (35% versus 71%, P = 0.007) and the adhesion score (0.38 versus 0.79, P = 0.009) were significantly lower in the alginate gel group than in the controls. The abscess rate was higher (46% versus 18%, P = 0.030) in the hyaluronate carboxymethyl cellulose group than in the controls and unchanged in the alginate gel group.

Conclusions

While reducing adhesion formation, ultrapure alginate gel does not interfere with the development of colonic anastomotic strength during the crucial early healing period.     

Hepatosplenic T Cell Lymphoma

A 26 year old lady came with intermittent fever since eight months. She also complained of abdominal pain and decreased appetite for six months. She had swelling of feet and distension of abdomen due to ascites since one month. There was history of jaundice one month back. On radiological examination, hepatomegaly with dilated portal vein, massive splenomegaly and ascites without any lymphadenopathy was noted. Chest X-ray was normal. Blood examination and bone marrow studies were inconclusive. We received her liver biopsy, which showed normal architecture and sinusoidal infiltration by a monomorphic population of small to intermediate sized lymphoid cells. Portal tracts were free of such infiltrate. These lymphoid cells were LCA, CD3, CD43 positive and negative for CD20, CD34, CD4, CD8 and c-kit. Based on all these features, a diagnosis of Hepatosplenic T cell lymphoma was made. She was treated symptomatically, however she died within two months of diagnosis.