Philip H. Rowe

Influence of drug:hydroxypropylmethylcellulose ratio, drug and polymer particle size and compression force on the release of diclofenac sodium from HPMC tablets

This study evaluates the relationship and influence of formulation and technological factors such as drug:hydroxypropylmethylcellulose (HPMC) ratio, particle size of the drug, particle size of HPMC and compression force, on drug release from matrices containing HPMC and diclofenac sodium as a model drug. The influence of these variables was assessed by multi-way analysis of variance. The results of the present study point out that the rate and mechanism of diclofenac sodium release from HPMC K15M matrices are mainly controlled by the drug:HPMC ratio. The drug and HPMC particle size also influence the drug release parameters, although to a lesser extent. Finally, the independence of the drug release from matrix tablets with respect to the compression force is reported.

Emergency re-admissions to hospital due to adverse drug reactions within 1 year of the index admission

AIM The proportion of re-admissions to hospital caused by ADRs is poorly documented in the UK. The aim of this study was to evaluate the impact of ADRs on re-admission to hospital after a period as an inpatient. METHODS One thousand patients consecutively admitted to 12 wards were included. All subsequent admissions for this cohort within 1 year of discharge from the index admission were retrospectively reviewed. RESULTS Of the 1000 patients included, 403 (40.3%, 95% CI 39.1, 45.4%) were re-admitted within 1 year. Complete data were available for 290 (70.2%) re-admitted patients, with an ADR contributing to admission in 60 (20.8%, 95% CI 16.4, 25.6%) patients. Presence of an ADR in the index admission did not predict for an ADR-related re-admission (10.5% vs. 7.2%, P=0.25), or re-admission overall (47.2% vs. 41.2%, P=0.15). The implicated drug was commenced in the index admission in 33/148 (22.3%) instances, with 37/148 (25%) commenced elsewhere since the index admission. Increasing age and an index admission in a medical ward were associated with a higher incidence of re-admission ADR. The most frequent causative drugs were anti-platelets and loop diuretics, with bleeding and renal impairment the most frequent ADRs. Over half (52/91, 57.1%) of the ADRs were judged to be definitely or possibly avoidable. CONCLUSIONS One fifth of patients re-admitted to hospital within 1 year of discharge from their index admission are re-admitted due to an ADR. Our data highlight drug and patient groups where interventions are needed to reduce the incidence of ADRs leading to re-admission.

Adverse drug reactions as a cause of admission to an acute medical assessment unit: a pilot study

Background: In this pilot study, we have investigated the frequency of adverse drug reaction (ADR)‐related admissions to an acute medical assessment unit. Although ADRs are thought to be responsible for 5% of hospital admissions, there have been no recent studies in the U.K.

The effects of compression rate and force on the compaction properties of different viscosity grades of hydroxypropylmethylcellulose 2208

Abstract The effects of compression speed and force on the compaction properties of four viscosity grades of hydroxypropylmethylcellulose 2208 (HPMC K100, HPMC K4M, HPMC K15M, HPMC K100M) have been assessed. The tensile strengths of their tablets, the energies involved in compaction, mean yield pressures, elastic recoveries and the contribution of the elastic and plastic energies to the gross energies have been evaluated using a compaction simulator. For each viscosity grade of HPMC, an increase in compression speed from 15 to 500 mm/s generally decreased the tensile strength of the tablets. The tensile strengths of HPMC Kl00 tablets were more sensitive to changes in compression speed than those of the other grades. Tablets of HPMC K100 had the highest tensile strength at any compression force or speed. An increase in compression speed from 15 to 500 mm/s resulted in an increase in the mean yield pressure of HPMCs. The highest elastic recoveries were found for compacts made at 500 mm/s at each viscosity grade (48.0, 28.1, 49.8 and 50.0% for HPMC K100, HPMC K4M, HPMC K15M and HPMC K100M, respectively). At each compression speed, HPMC K4M had the lowest elastic recovery. For each viscosity grade of HPMC, an increase in compression force from 5 to 10 kN resulted in an increase in elastic recovery; above a force of 10 kN the elastic recovery decreased for each HPMC except HPMC K4M. An increase in compression force and speed increased the percentage contribution of the elastic energies of the gross energies for the different grades of HPMC. For example, for HPMC K4M the percentage contribution of the elastic energies of the gross energies were 12.4 and 39.9% for compression forces of 5 and 20 kN, respectively, and for compression speeds of 15 and 500 mm/s were 16.1 and 34.2%, respectively.

Effects of surface roughness and chrome plating of punch tips on the sticking tendencies of model ibuprofen formulations

The sticking of three model ibuprofen–lactose formulations with respect to compaction force and the surface quality of the upper punch were assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single‐punch tablet press. Two sets of 12.5‐mm flat‐faced punches were used to evaluate the influence of surface quality. A third set of chrome‐plated tooling was also used. Surface profiles (Taylor Hobson Talysurf 120) of the normal tooling upper punches indicated a large difference in quality. The punches were subsequently classified as old (Ra = 0.33 μm) or new (Ra = 0.04 μm) where Ra is the mean of all positive deviations from zero. Surface profiles of sample tablets were also obtained. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. Punch surface roughness, compaction force and the blend composition were all significant factors contributing to sticking. Chrome plating of punch faces increased sticking at a low compaction force but decreased sticking at higher forces. Surface roughness of the tablets did not correlate with the corresponding data for sticking, indicating that this is not a suitable method of quantifying sticking.

Effect of lubricant type and concentration on the punch tip adherence of model ibuprofen formulations.

A model formulation, comprising ibuprofen and direct compression lactose (Tablettose 80) was used to assess the influence of two lubricants, magnesium stearate and stearic acid, on punch tip adherence. Lubricant concentrations were varied from 0.25% to 2% w/w. Formulations in the presence and absence of 0.5% w/w colloidal silica (Aerosil 200) were examined, to assess the influence of the glidant on the anti‐adherent effects of the lubricants. Differential scanning calorimetry (DSC) was used to examine the effect of the lubricants on the melting temperature of ibuprofen. Tablets were compacted using a single punch tablet press at 10 kN using hard chrome‐plated punches or at 40 kN using uncoated steel punches, tooling was 12.5‐mm diameter in each case. The upper punch faces were characterized by obtaining Taylor Hobson Talysurf surface profiles. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. At low concentrations of each lubricant, the levels of sticking observed were similar. Whilst sticking increased at magnesium stearate concentrations above 1%, sticking with stearic acid remained relatively constant at all concentrations. DSC revealed that the melting temperature of ibuprofen was lowered by the formation of eutectic mixtures with both lubricants. However, the onset temperature of melting and melting point were lowered to a greater extent with magnesium stearate compared with stearic acid. When using uncoated tooling at 40 kN, the deleterious effects of magnesium stearate on the tensile strength of the tablets also contributed to sticking. When using chrome‐plated punches at 10 kN, the tensile strength reduction by the presence of magnesium stearate was less pronounced, as was the level of sticking.

Effect of punch tip geometry and embossment on the punch tip adherence of a model ibuprofen formulation

The sticking of a model ibuprofen‐lactose formulation with respect to compaction force, punch tip geometry and punch tip embossment was assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single‐punch tablet press. Three sets of ‘normal’ concave punches were used to evaluate the influence of punch curvature and diameter. The punches were 10, 11 and 12 mm in diameter, respectively. The 10‐mm punch was embossed with a letter ‘A’ logo to assess the influence of an embossment on sticking. Flat‐faced punches (12.5 mm) were used for comparison with the concave tooling. Surface profiles (Taylor Hobson Talysurf 120) of the upper punch faces were obtained to evaluate the surface quality of the tooling used. Following compaction, ibuprofen attached to the upper punch face was quantified by spectroscopy. Increasing punch curvature from flat‐faced punches to concave decreased sticking. Altering punch diameter of the concave punches had no effect on sticking when expressed as μg mm−2. The embossed letter ‘A’ logo increased sticking considerably owing to the probable concentration of shear stresses at the lateral faces of the embossed logo.

The Influence of Moisture Content on the Consolidation Properties of Hydroxypropylmethylcellulose K4M (HPMC 2208)

The effect of moisture content, compression speed and compression force on the compaction properties of HPMC K4M has been evaluated.

The effect of moisture on the Heckel and energy analysis of hydroxypropylmethylcellulose 2208 (HPMC K4M)

The influence of moisture content on the Heckel analysis, energy analysis and strain‐rate sensivity of hydroxyproplymethylcellulose 2208 (HPMC K4M) has been evaluated.

Pharmaceutics: The Effects of Lag-time and Dwell-time on the Compaction Properties of 1:1 Paracetamol/microcrystalline Cellulose Tablets Prepared by Pre-compression and Main Compression

The effects of lag‐time and dwell‐time on the compaction properties of tablets compressed from a 1:1 blend of paracetamol and microcrystalline cellulose have been examined using a compaction simulator.