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.     

Bubaline Aortic Matrix: Histologic,Imaging, Fourier Transform Infrared Spectroscopic Characterization and Application into Cattle Abdominal Hernia Repair

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Extracellular matrix (ECM) scaffolds have been shown to promote constructive remodeling response into a host....     

Influence of etoricoxib on anticonvulsant activity of phenytoin and diazepam in experimental seizure models in mice

Objectives Our aim was to investigate the effect of etoricoxib on the anticonvulsant activity of phenytoin and diazepam against seizure models in mice. In addition the acute adverse effect of etoricoxib was assessed with a chimney test. Methods The maximal seizure pattern was induced in mice by giving an alternating current of 50 mA for 0.2 s, while chemical seizures were induced by intraperitoneal injection of pentylenetetrazole at its CD97 dose (97% convulsive dose for the clonic phase). Test drug was administered 45 min before the electrical or chemical induction of seizures in combination with conventional antiepileptics. The ability of the test drug to reduce or abolish the extensor phase of maximal electroshock and clonic‐type seizures in the chemical induction method was selected as anti‐seizure criteria. Key findings Concurrent treatment with etoricoxib at an oral dose of 10 mg/kg reduced the anticonvulsant potency of phenytoin. The protective effects of diazepam against pentylenetetrazole‐induced convulsions was significantly increased and the mortality rate was reduced by concurrent treatment with etoricoxib (10 mg/kg p.o.) when compared with diazepam groups. No neurotoxic effect was observed with etoricoxib (10 mg/kg p.o.) and it had no impact on motor coordination in the chimney test in mice. Etoricoxib applied at its highest dose (10 mg/kg) significantly enhanced the free plasma levels of diazepam whereas the free plasma levels of phenytoin were significantly reduced. Conclusions The obtained results suggest that the preferential cyclooxygenase‐2 inhibitor etoricoxib significantly reduced the anticonvulsant action of phenytoin and significantly increased the beneficial action of diazepam against maximal electroshock and pentylenetetrazole‐induced convulsions in a mouse model.     

The impact of packed red blood cell transfusion on clinical outcomes in patients with septic shock treated with early goal directed therapy

Background:

The optimal hemoglobin level and transfusion threshold in patients with septic shock treated with an early, goal oriented approach to resuscitation remains unknown.

Aims:

To assess the impact of packed red blood cell (PRBC) transfusion on clinically relevant outcomes in patients with septic shock treated with early goal directed therapy (EGDT).

Settings and Design:

Retrospective cohort study of 93 patients who presented with septic shock, to a single center academic intensive care unit and received EGDT.

Materials and Methods:

Data were collected on patients identified via the Surviving Sepsis Campaign Chart Review database and linked to Project IMPACT database. The PRBC group and no PRBC group were compared by the Pearson chi-square and Fisher’s exact test to analyze statistical significance.

Results:

The PRBC group had a mortality of 41.2% vs. 33.9% in the no PRBC transfusion group (P = NS). The PRBC group also had more mechanical ventilation days (11.2 days vs. 5.0 days, (P ≤ 0.05), longer hospital length of stay (25.9 days vs. 12.5 days, (P ≤ 0.05), and longer intensive care unit length of stay (11.4 days vs. 3.8 days, (P ≤ 0.05).

Conclusions:

In this retrospective cohort study, transfusion of PRBCs was associated with worsened clinical outcomes in patients with septic shock treated with EGDT. Further studies are needed to determine the impact of transfusion of PRBC within the context of early resuscitation of patients with septic shock, as the beneficial effects gained by an early and goal oriented approach to resuscitation may be lost by the negative effects associated with PRBC transfusion.     

Benign monoclonal B cell lymphocytosis--a benign variant of CLL: clinical, immunologic, phenotypic, and cytogenetic studies in 20 patients

From 1951 through 1978, we have seen 20 cases of stage O chronic lymphocytic leukemia (CLL) without disease progression for 6.5-24 years. The cohort included 7 males and 13 females, aged 48-77 years at the time of diagnosis. None presented with anemia, thrombocytopenia, or neutropenia nor developed cytopenias during follow-up. Mean total lymphocyte count in these patients was 20,100/microL, with ranges from 10,000 to 43,700 at the time of diagnosis, and was 20,600, with ranges from 1,000 to 47,200, at last follow-up. Of 12 patients studied, 8 and 4 were phenotyped as heavy chain mu delta- and mu-type, respectively, with 7 kappa- and 4 gamma-type (no light chain was detectable in one patient). Of 13 patients studied, one had a slightly elevated IgG level and two had slightly depressed serum IgA and IgM levels. All patients had positive delayed hypersensitivity responses to at least one of five skin test antigens. Each of seven patients studied for an in vitro leukocyte thymidine uptake had a low level of [3H]thymidine incorporation. Nine of 12 patients studied had elevated total T cells, and the remaining 3 had normal T cell counts. In vitro unseparated lymphocyte response to phytohemagglutinin showed normal kinetics of DNA synthesis, with a peak response on day 3 or 4 of culture in 4 and slightly or moderately depressed and/or delayed kinetics in 8 patients studied. Cytogenetic analyses by Q- or G-banding techniques of polyclonal B cell mitogen-stimulated lymphocytes in all six patients studied showed normal karyotypes. These data are consistent with a previously undescribed syndrome involving a monoclonal B cell lymphocytosis, a prolonged asymptomatic or benign clinical course, and essentially normal humoral and cellular immunity and normal karyotype. Our observations indicate that these 20 patients with stage O CLL have a benign clinical course and that they may also be designated as benign monoclonal B cell lymphocytosis ( BMBL ), a benign variant of CLL.     

Investigate the effect of solvents on wet granulation of microcrystalline cellulose using hydroxypropyl methylcellulose as a binder and evaluation of rheological and thermal characteristics of granules

Wet granulation is the most commonly used technique in the pharmaceutical industry for delivering oral solid dosage forms. In wet granulation, the binder solvent is one of the critical factors affecting granule properties. In the current study, an attempt was made to investigate the effect of solvents (aqueous and hydro-alcoholic) on thermal and flow properties of Microcrystalline Cellulose (MCC) granules prepared using two different grades of Hydroxypropyl Methylcellulose (HPMC), which served as an effective binder. The granulation endpoint was evaluated using thermal effusivity sensor. Rheometer and Modulated Differential Scanning Calorimetry (mDSC) was used to study the flow and thermal properties of wet and dried granules. Furthermore, physical characterization was carried out by granule strength, particle size distribution and tablet hardness for all granules under the study. Thermal effusivity sensor results indicate 55% w/w concentration of binder solution as the endpoint by measuring thermal effusivity for both binders. Additionally, powder rheometer results show that the wet granules of hydro-alcoholic batches show greater resistance to flow whereas the dried granules display excellent flow characteristics as evident from Basic flowability energy values and specific energy values. Permeability results suggest that the granules formed with hydro-alcoholic binder solvent exhibit better porosity and permeability. Tablet hardness data showed that tablets formulated using hydro-alcoholic solvent granules have greater hardness than tablets formulated using water based solvent granules. The granule strength for water based granules is relatively higher than that of hydro-alcoholic based granules. mDSC thermograms show a sharp rise in enthalpy value at 55% w/w binder solution which is indicative of a more significant amount of solvent being present on the surface of granules and formation of optimal granules. To summarize, we have determined a technique to measure endpoint determination and simultaneously investigate the role of solvent systems on the rheology of MCC granules, which could assist in selecting an appropriate solvent system for granulation.     

Primary malignant melanoma presenting as superior mediastinal mass

Malignant melanoma accounts for 1.5% of all cancers, and arises from a preexisting nevus in 40% of cases. Skin is the most common site for primary malignant melanoma. We present an extremely rare case of primary malignant melanoma presenting as a superior mediastinal mass.     

Excessive dynamic airway collapse for the internist: new nomenclature or different entity?

Excessive dynamic airway collapse (EDAC) refers to abnormal and exaggerated bulging of the posterior wall within the airway lumen during exhalation. This condition is pathological if the reduced airway lumen is <50% of the normal. It is a relatively new disease entity that is recognised more easily now with the increased use of multi-detector row CT. EDAC is often asymptomatic and diagnosed incidentally. Although the term excessive dynamic airway collapse is often used interchangeably with tracheobronchomalacia, both entities represent morphologically and physiologically distinct processes. Considering the confusion between the two entities, the prevalence of stand-alone EDAC remains unclear. The prevalence of tracheobronchomalacia and EDAC depends upon the patient population, associated comorbidities and underlying aetiologies, diagnostic tools used and criteria used to define the airway collapse. This review defines EDAC and describes its pathophysiology, precipitating factors, associated symptoms and potential treatments.