Assessing the Impact of Punch Geometries on Tablet Capping Using a Newly Proposed Capping Index.

PURPOSE: Increased tablet anisotropy could lead to increased tablet capping propensity. Tooling design variables such as cup depth could serve as a key player for inducing tablet anisotropy. METHODS: A new capping index (CI) consisting of the ratio of compact anisotropic index (CAI) and material anisotropic index (MAI) is proposed to evaluate tablet capping propensity as a function of punch cup depth. CAI is the ratio of axial to radial breaking force. MAI is the ratio of axial to radial Young's modulus. The impact of various punch cup depths [flat face, flat face beveled edge, flat face radius edge, standard concave, shallow concave, compound concave, deep concave, and extra deep concave] on the capping propensity of model acetaminophen tablets was studied. Tablets were manufactured at 50, 100, 200, 250, and 300 MPa compression pressure at 20 RPM on different cup depth tools using Natoli NP-RD30 tablet press. A partial least squares model (PLS) was computed to model the impact of the cup depth and compression parameters on the CI. RESULTS: The PLS model exhibited a positive correlation of increased cup depth to the capping index. The finite elemental analysis confirmed that a high capping tendency with increased cup depth is a direct result of non-uniform stress distribution across powder bed. CONCLUSIONS: Certainly, a proposed new capping index with multivariate statistical analysis gives guidance in selecting tool design and compression parameters for robust tablets.

Muscle fatigue response of rotator cuff muscles in different postures.

INTRODUCTION: Muscle fatigue is a leading cause of rotator cuff (RC) pathologies. Scapular orientation affected by changes in the thoracic spine account for differences in body postures leading to altered RC muscle activation. This posture-related alteration in RC muscle activation and its fatigue response needs to be analyzed. MATERIALS AND METHODS: This study included 50 healthy shoulders with no coexisting spine pathologies. Raw data were recorded using electromyography sensors for RC muscles during two isometric maneuvers of abduction and external rotation, performed at 30% maximum voluntary contraction at 30°, 45°, and 90° arm elevation in sitting and standing. The raw data were analyzed in DataLITE® software, and the mean power frequency (MPF) was extracted to analyze the fatigue response of RC muscles. The Wilcoxon signed-rank test and Kruskal-Wallis test with Bonferroni corrections analyzed fatigue differences between postures and various activities. P < 0.05 was considered significant for the results. RESULTS: Supraspinatus muscle demonstrated significant fatigue at 90° of arm elevation in standing as compared to sitting (MPF -5.40: -5.41; P = 0.03) posture. Between the three elevation angles, all the RC muscles showed increased fatigue at 90° (MPF range -5.22 to -6.64). When compared between abduction and external rotation, only infraspinatus showed fatigue in external rotation (MPF range -5.42 to -6.08). Among all the three RC muscles, infraspinatus showed the maximum fatigue of MPF -6.64 when compared to supraspinatus -5.22 and teres minor -5.36. CONCLUSION: The findings indicate that alterations in the body postures and different elevation angles affect the RC muscles' fatigue response.

A systematic review of the effectiveness of wrist manipulative therapy in patients with lateral epicondylitis.

STUDY DESIGN: Systematic review. INTRODUCTION: Several treatment methods treat lateral epicondylitis, but there is no consensus regarding the most effective method. Research has suggested that joint mobilizations may help recover patients with lateral epicondylitis. PURPOSE OF THE STUDY: To determine if wrist joint manipulations effectively improve pain, grip strength, ROM, and functional outcome in adults with lateral epicondylitis. METHODS: Searches were performed in 6 databases to identify relevant clinical trials. Three reviewers independently extracted data and assessed the methodological quality using the PEDro scale. Standard data were extracted and summarized. RESULTS: A total of 4 studies met the inclusion criteria. A best-evidence synthesis was used to summarize the results. The included studies found effectiveness in favor of wrist manipulations given for at least 3 weeks to reduce pain in lateral epicondylitis against comparison groups comprising ultrasound, laser, friction massage, and exercises. Functional outcomes varied considerably among studies. Grip strength showed varied results, and no effect was seen on wrist ROM. CONCLUSION: The evidence is convincing that wrist joint manipulations positively affect pain in the short term, compared to comparison groups in the management of lateral epicondylitis. Future high-quality studies are recommended.

Compression-decompression modulus (CDM) - an alternative/complementary approach to Heckel's analysis.

The novel modulus-based approach was developed to characterize the compression behavior of the materials and how it results into tablet mechanical strength (TMS) of the final tablet. The force-displacement profile for the model materials (Vivapur® 101, Starch 1500®, Emcompress®, and Tablettose® 100) was generated at different compression pressures (100, 150, and 200 MPa) and speeds (0.35, 0.55, and 0.75 m/s) using compaction emulator (Presster™). A generated continuous compression profile was evaluated with Heckel plot and the proposed material modulus method. The computed compression parameters were qualitatively and quantitatively correlated with TMS by principal component analysis and principal component regression, respectively. Compression modulus has negatively correlated, while decompression modulus is positively correlated to TMS. Proposed modulus descriptors are independent of particle density measurements required for the Heckel method and could overcome the limitations of the Heckel method to evaluate the decompression phase. Based on the outcome of the study, a two-dimensional compression and decompression modulus classification system (CDMCS) was proposed. The proposed CDMCS could be used to define critical material attributes in the early development stage or to understand reasons for tablet failure in the late development stage.

Optimized L-SNEDDS and spray-dried S-SNEDDS using a linked QbD-DM3 rational design for model compound ketoprofen.

A QbD-DM3 strategy was used to design ketoprofen (KTF) optimized liquid (L-SNEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS). Principal component analysis was used to identify the optimized L-SNEDDS containing Capmul® MCM NF, 10 % w/w; Kolliphor® ELP, 60 % w/w; and propylene glycol, 30 % w/w. The S-SNEDDS was manufactured by spray-drying a feed dispersion prepared by dissolving the optimized KTF-loaded L-SNEDDS in an ethanol-Aerosil® 200 dispersion. A Box Behnken design was employed to evaluate the effect of drug concentration (DC), Aerosil® 200 concentration (AC) and feed rate (FR) on maximizing percent yield (PY) and loading efficiency (LE). The optimal levels of DC, AC, and FR were 19.9 % w/w, 30.0 % w/w, and 15.0 %, respectively. The optimized S-SNEDDS was amorphous, and its dissolution showed a 2.37-fold increase in drug release compared to KTF in 0.1 HCl. An optimized independent spray-dried S-SNEDDS verification batch showed that the predicted and observed PY and LE were 70.49 % and 92.49 %, and 70.02 % and 91.27 %, respectively. The optimized L-SNEDDS and S-SNEDDS also met their quality target product profile criteria for globule size <100 nm, polydispersity index < 0.400, emulsification time < 30 s, and KTF L-SNEDDS solubility 100-fold greater than its water solubility.

Comparison of Single and Combined Treatment with Exercise Therapy and Collagen Supplementation on Early Knee Arthritis among Athletes-A Quasi-Randomized Trial.

Athletic injuries are commonly implicated in the development of early osteoarthritic (EOA) changes in the knee. These changes have a significant impact on athletic performance, and therefore the early detection of EOA is paramount. The objective of the study is to assess the impact of different interventions on individuals with EOA, particularly focusing on recreational athletes. The study aims to evaluate the effectiveness of three treatment groups in improving various aspects related to knee EOA, including pain, range of motion, strength, and function. A study was undertaken with 48 recreational athletes with EOA who were assigned to one of three groups by the referring orthopedic surgeon: collagen (Col), exercise (Ex), or collagen and exercise (ColEx) groups. All the participants received their respective group-based intervention for 12 weeks. Visual analog scale (VAS), knee flexion range of motion (ROM) knee flexors and extensors strength, and KOOS were assessed at baseline, and after 4 weeks, 8 weeks, and 12 weeks of intervention. VAS for activity improved in all treatment groups, with no difference between groups. The between-group analysis for knee ROM revealed a significant difference (p = 0.022) in the Col vs. Ex group at 12 weeks. The knee flexor and extensor strength and the KOOS scores improved considerably in the Ex and the ColEx group (p < 0.05) at 12 weeks. Exercise therapy improved pain, strength and function in subjects with EOA, whereas the association of collagen seems to have accentuated the effects of exercise in bringing about clinical improvements.

Negative porosity issue in the Heckel analysis: A possible solution.

A parameterization of compaction simulator generated dynamic compression profile with a few grams of powder provides important information about the material deformation and compact elasticity. The Heckel equation is by far the most popular choice among pharmaceutical scientists for such parametrization. A general approach of Heckel analysis uses pycnometric powder density (ρP0) for relative density calculation. However, as 'in-die' tablet bulk density at applied compression pressure (ρBP) becomes greater than or equal to the measured ρP0, the general approach typically poses a negative porosity challenge at high compression pressure regions. It is only theoretically possible to have a tablet with zero or negative porosity. Negative porosity may be detected during 'in-die' compression analysis, but it will not exist after ejection of the tablet in practical aspect. Thus, the present work proposes a new approach to using pycnometric tablet density (ρPP) in the relative density calculations of Heckel analysis. This ρPP may be a better representation of actual tablet particle volume, as it is composed of non-accessible intra-particulate pores, which are broken under applied compression pressure. A new approach showed its immunity for Heckel high-pressure negative porosity. It enables the utilization of the compression and decompression phases of dynamic compression profiles to evaluate macroscopic compaction performance. The proposed approach was validated with a reported modified Heckel approach. The Heckel parameters computed with both methodologies for microcrystalline cellulose and lactose were not statistically different. However, a modified Heckel approach was unable to compute Heckel parameters of poorly compacting starch unlike the new approach. A modified Heckel approach became invalid during starch compaction at low compression pressures (below 400 MPa), where starch was forming weaker but still intact tablets. Certainly, a complete Heckel profiling with a new approach could save time and costs in an early development stage for designing and screening scientifically based lead prototype formulations.