Characterization Of Excipients Research Articles

Preparation and Characterization of Co-Processed Mannitol and Sorbitol Using NanoCrySP Technology.

Particle engineering of excipients, at sub-particulate level using co-processing, can provide high functionality excipients. NanoCrySP technology has been recently explored as a novel approach for the generation of nanocrystalline solid dispersion of poorly soluble drugs, using spray drying process. The purpose of the present study was to generate co-processed mannitol and sorbitol (SD-CSM) using NanoCrySP technology having similar composition to commercial co-processed excipient (Compressol® SM, CP). The characterization of excipients was performed to evaluate their various physicomechanical properties. The sub-micron crystallite size of sorbitol in the matrix of mannitol was determined using the Williamson-Hall equation and Halder-Wagner equation. The reduction in crystallite size of sorbitol and mannitol, lower melting point, and lower heat of fusion of SD-CSM could be responsible for excellent compactibility, better tabletability, and comparable compressibility with respect to CP. This was confirmed by the compressibility-tabletability-compactibility (CTC) profile and Heckel plot analysis. Overall, SD-CSM generated using NanoCrySP technology improved functionalities of excipients over CP and would be useful for direct compression application.

Analytical approach for lubricant characterization of excipients using the surface replication method

Lubricants are indispensable pharmaceutical ingredients for preventing tableting failure due to powder adhesion to the die wall. The impact of lubricants was evaluated with use of the Binding Identification for Net Detriment (BIND) surface replication method. Raloxifene hydrochloride (RH) was selected as a model chemical with high adhesion, and four commercially available tablet lubricants – stearic acid, sodium stearyl fumarate, calcium stearate, and magnesium stearate – were used for RH formulation. BIND was applied to the die wall to analyze the effect of various lubricants on binding properties. The preparations without lubricants showed poor tableting properties as evidenced by as much as 61.7% powder adhesion density. Lubricants significantly altered the binding properties, yielding powder adhesion densities of 40.2% (stearic acid), 29.7% (stearyl sodium fumarate), 23.0% (calcium stearate), and 13.6% (magnesium stearate). Evaluation of three grades of magnesium stearate resulted in a two-fold difference between the highest and the lowest powder adhesion density. Throughout the work, conventional methods including visual observations and measurement of ejection force were unable to provide qualitative/quantitative evaluations. The ejection process depends on both axial force and radial force; however, the ejection force show only the axial force. At the same time, visual observation could release significant qualitative results. However, BIND allowed qualitative and quantitative analysis of the binding properties. BIND is a promising assessment method for analyzing the impacts of various lubricants on binding properties and for optimizing RH formulations.

Characterization of Excipient and Tableting Factors That Influence Folic Acid Dissolution, Friability, and Breaking Strength of Oil- and Water-Soluble Multivitamin with Minerals Tablets

The goal of this study is to characterize the formulation and processing factors that influence folic acid dissolution from oil- and water-soluble multivitamin with minerals tablet formulations for direct compression. The following parameters were studied: bulk filler solubility, soluble to insoluble bulk filler ratio, triturating agent (preblending carrier) solubility, disintegrant usage, compression pressure, and folic acid particle size. Folic acid particle size was determined by using light microscopy, and surface area was measured by using BET adsorption. The tablets were compressed on an instrumented Stokes B2 tablet press, and the friability, weight variation, and dissolution were measured according to USP methods, along with tablet breaking strength. In summary, we found the following factors to be critical to folic acid dissolution: bulk filler solubility (soluble fillers, such as maltose, increase folic acid dissolution); disintegrant amount (levels less than 0.4% (w/w) are ineffectual, whereas levels greater than 1.2% (w/w) did not further increase dissolution); and compression force (generally, maltose produce harder tablets). In addition, folic acid dissolution was less affected by changes in compaction pressure when a “super” disintegrant and maltose, as a bulk filler, were used. It was determined that the trituration agent did not play a significant role in folic acid dissolution. In the range of parameters studied, statistical analysis found no significant interactions between the parameters studied, which means they act independently in an additive manner. The results also show that no one factor is completely responsible for dissolution failure. Thus, it is the combination of formulation factors and processing conditions that collectively add up to produce dissolution failure; however, the use of a disintegrant and a soluble filler such as maltose can make a formulation more robust to the inevitable changes that can occur during commercial production.

Evaluation of Two Dextrose-Based Directly Compressible Excipients

The objectives of this research were to evaluate the physical properties and compaction behavior of two dextrose-based directly compressed excipients. Anhydrous theophylline (10% w/w) was used as a drug model, Emdex and or Maltrin M510 (89.5% w/w) were used as diluent, and magnesium stearate (0.5% w/w) was used as lubricant. Direct compression and wet granulation methods were used for preparing the compacts. In general, the wet granulation method reduced the density of the mixture and consequently its flow rate compared to the mixture prepared only by solid-solid mixing. All formulations were compressed at four different compres-sional forces and at a target weight of 450 mg ± 5%. Tablets obtained were different in physical properties and mechanical strength based on type of excipient used and methods of tablet preparation (direct compression versus wet granulation). Compacts prepared from Maltrin M510 had a longer disintegration time and slower drug release than compacts of the same composition but prepared with Emdex. Disintegration time and drug dissolution from tablets containing Maltrin M510 as diluent and prepared by wet granulation appeared to be controlled by a “gel” layer formation around the tablets and not by the tablets porosity. This study demonstrates that full characterization of excipients is needed because a different manufacturing process for the same excipients may produce differences in the pharmaceutical products.