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.

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.

Evaluating the effect of glidants on tablet sticking propensity of ketoprofen using powder rheology.

Punch sticking has been a leading drawback that has challenged successful tablet manufacturing since its initial conception. Due to the capricious nature of the complication, this can arise during any phase of the development process. Even now, identifying such a problem is a prerequisite during the initial stage of development. The present study evaluated the role of Aerosil®200, talc, and Syloid®244 as glidants in varying amounts ranging from 0.0 percent to 2.0 percent w/w on tablets sticking relatively to five different metal surfaces, with ketoprofen as the model drug. Powder rheology is a predictable technique used to calculate the sticking index. The sticking index of each formulation in comparison to each metal coupon was identified by calculating the kinematic angle of internal friction and the angle of wall friction using the shear cell test and wall friction test, respectively. Interestingly, glidants were found to reduce the sticking propensity of the powder blend in a concentration-dependent manner. In addition, the compression study validated the expected sticking tendency ranking order. According to the research data, the sticking index could effectively be utilized to envisage the possibility of tablet sticking, i.e., by selecting the formulation's excipient and their percentages or selecting appropriate punched metal surfaces in the tableting process.

Predicting lubricants effect on tablet sticking using ketoprofen as model drug and evaluating sticking propensity using different metals and powder rheology.

Tablet sticking occurrence is a persistent, costly, and time-consuming problem that needs to be resolved. Predicting the sticking tendency of a new formulation has been very difficult during the development batches because of short runs and limited data. A model formulation comprising ketoprofen and microcrystalline cellulose was used to predict the effect of magnesium stearate and sodium stearyl fumarate on the occurrence of tablet sticking relative to different punch metals. Lubricant amounts were varied from 0.0% to 2.0 %w/w. Five different metal coupons were used to represent punch metals. The sticking index (SI) of each formulation relative to each metal coupon was determined by measuring angle of internal friction and angle of wall friction by performing shear cell test and wall friction test, respectively. The SI was used to predict each formulation's sticking tendency rank order relative to metal coupon. Both lubricants show a decrease in the powder blend's sticking propensity with increased lubricant concentration. The predicted sticking propensity rank order was then validated by the compression study. The result suggests that the SI can be used to predict tablet sticking, such as by changing the composition of the formulation or changing the punch metal during tablet compression.

Preparation, Optimization and Evaluation of Chitosan-Based Avanafil Nanocomplex Utilizing Antioxidants for Enhanced Neuroprotective Effect on PC12 Cells.

(1) Introduction: in recent decades, interdisciplinary research on the utilization of natural products as "active moiety carriers" was focused on due to their superior safety profile, biodegradability, biocompatibility and the ability for sustained or controlled release activity. The nano-based neuroprotective strategy is explored as an imperative treatment for diabetic neuropathy (DN). Avanafil (AV), that selectively inhibits the degradation of cGMP-specific phosphodiesterase, thereby increasing the levels of cGMP, makes a decisive mediator for cytoprotection. (2) Methods: AVnanocomplex formulations were prepared by a modified anti-solvent precipitation method and the method was optimized by Box-Behnken design. An optimized formulation was characterized and evaluated for various in vitro parameters; (3) results:based on the desirability approach, the formulation containing 2.176 g of chitosan, 7.984 g of zein and 90% v/v ethanol concentration can fulfill the prerequisites of optimum formulation (OB-AV-NC).OB-AV-NC was characterized and evaluated for various parameters. The neuroprotective mechanism of AV was evaluated by pretreatment of PC12 cells with plain AV, avanafil nanocomplex (NC) without antioxidants (AV-NC) and with antioxidants (α-Lipoic acid LP; Ellagic Acid EA), AV-LP-EA-Nanocomplex has also shown considerable attenuation in intracellular reactive oxygen species (ROS) and lipid peroxidation with a significant increase in the PC 12 viability under HG conditions in comparison to pure AV; (4) conclusion: the nanocomplex of AV prepared to utilize natural polymers and antioxidants aided for high solubility of AV and exhibited desired neuroprotective activity.This can be one of the promisingstrategy to translate the AV nanocomplex with safety and efficacy in treating DN.

Chitosan as Functional Biomaterial for Designing Delivery Systems in Cardiac Therapies.

Cardiovascular diseases are a leading cause of mortality across the globe, and transplant surgeries are not always successful since it is not always possible to replace most of the damaged heart tissues, for example in myocardial infarction. Chitosan, a natural polysaccharide, is an important biomaterial for many biomedical and pharmaceutical industries. Based on the origin, degree of deacetylation, structure, and biological functions, chitosan has emerged for vital tissue engineering applications. Recent studies reported that chitosan coupled with innovative technologies helped to load or deliver drugs or stem cells to repair the damaged heart tissue not just in a myocardial infarction but even in other cardiac therapies. Herein, we outlined the latest advances in cardiac tissue engineering mediated by chitosan overcoming the barriers in cardiac diseases. We reviewed in vitro and in vivo data reported dealing with drug delivery systems, scaffolds, or carriers fabricated using chitosan for stem cell therapy essential in cardiac tissue engineering. This comprehensive review also summarizes the properties of chitosan as a biomaterial substrate having sufficient mechanical stability that can stimulate the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering.