Biomedical subjects

Changquan Calvin Sun

Publications and source records attributed to Changquan Calvin Sun.

8 recordsLinked to original sources

PubMed2026

A correction factor for bridging compaction simulator and different roller compactors.

Roller compaction (RC) is an important dry granulation technique. Since pilot and commercial scale roller compactors, which operate continuously on a large scale, usually require kilograms of material per run, formulation and process development directly on such roller compactors is not practical. In contrast, a compaction simulator (CS) can produce ribblets, also known as "slugs", using only a few grams of material with sinusoidal displacement profile replicating the motion of a specific point on the roll surface. Thus, it is possible to develop RC formulation and process in laboratory using a CS-based material-sparing approach. However, because of the inherently different configurations for applying pressure between die compression and roll compression, translating uniaxial pressure from CS experiments to roll pressure during RC is often unreliable, leading to significant uncertainties in the critical quality attributes of ribbons, such as ribbon solid fraction (or porosity) and mechanical strength. The objective of this study was to identify a correction factor (Kp = uniaxial die compression pressure/roll pressure), by correlating the compressibility profiles from CS and a roller compactor of interest, to enable more reliable process translation from CS to roller compactor. In this study, a Kp value of 0.5 was determined for Alexanderwerk WP120 and validated for Gerteis Mini-Pactor and Bepex Pharmapactor. This value may serve as a starting point for translating the optimal compaction pressure identified based on CS investigation to common roller compactors, requiring only minor adjustments to attain optimal RC process parameters (i.e., roll force and roll gap) for a chosen roller compactor.

Drug Compounding↗

PubMed2006

A material-sparing method for simultaneous determination of true density and powder compaction properties--aspartame as an example.

True density results for a batch of commercial aspartame are highly variable when helium pycnometry is used. Alternatively, the true density of the problematic aspartame lot was obtained by fitting tablet density versus pressure data. The fitted true density was in excellent agreement with that predicted from single crystal structure. Tablet porosity was calculated from the true density and tablet apparent density. After making the necessary measurements for calculating tablet apparent density, the breaking force of each intact tablet was measured and tensile strength was calculated. With the knowledge of compaction pressure, tablet porosity and tensile strength, powder compaction properties were characterized using tabletability (tensile strength versus pressure), compactibility (tensile strength versus porosity), compressibility (porosity versus pressure) and Heckel analysis. Thus, a wealth of additional information on the compaction properties of the powder was obtained through little added work. A total of approximately 4 g of powder was used in this study. Depending on the size of tablet tooling, tablet thickness and true density, 2-10 g of powder would be sufficient for characterizing most pharmaceutical powders.

Aspartame↗

PubMed2006

Solid-state properties and crystallization behavior of PHA-739521 polymorphs.

PHA-739521 is an experimental compound that exhibits polymorphism. The two anhydrous crystal forms, I and II, are characterized using powder X-ray diffractometry, thermal analyses, moisture sorption gravimetry. Both Forms I and II are non-hygroscopic and are stable to compaction pressure. The melting temperature is about 152 degrees C for Form I and 168 degrees C for Form II. Forms I and II are enantiotropically related where Form I is more stable below a transition temperature of approximately 70 degrees C. Crystallization behavior of this compound from solutions and during heating is also studied. Information obtained is used to design an appropriate crystallization process to successfully manufacture desired polymorph at large scale.

Calorimetry, Differential Scanning↗

PubMed2006

Reduced tabletability of roller compacted granules as a result of granule size enlargement.

The mechanism for the frequently observed "loss of reworkability or tabletability" of dry-granulated (DG) powders was investigated in detail using microcrystalline cellulose (MCC). It was hypothesized that granule size enlargement is the primary mechanism to the phenomenon. Detrimental effects of size enlargement on tabletability of plastic materials are predictable based on the physical model of interparticulate bonding within a tablet. In absence of extensive fracture of particles/granules, larger particles/granules exhibit lower surface area available for bonding thus lower tensile strength when compressed under identical conditions. Size effects were first demonstrated using different grades of MCC powders, both whole and sieved, of different particle size distributions. Regardless grade and sieve fraction, larger particles always resulted in lower tabletability, that is, lower tensile strength at the same compaction pressure. It was subsequently shown that enlargement of granules also reduced powder tabletability regardless grade of MCC. Tabletability of sieved granules after roller compacted for one, two, and four times decreased monotonically with increasing granule size but independent of the total number of roller compaction. Moreover, tabletability of fine granules (44-106 microm) was higher than that of coarse MCC powder (Avicel PH-200). These results suggest that the primary mechanism for reduced tabletabilty of DG granules of MCC is granule size enlargement rather than "work-hardening."

Cellulose↗

PubMed2005

Evaluation of the effects of tableting speed on the relationships between compaction pressure, tablet tensile strength, and tablet solid fraction.

It is well known that compression speed can have significant effects on the compaction properties of pharmaceutical powders. This is a challenge during scale up and technology transfer when tableting speeds are significantly increased. This study examined the effects of tableting speed on the compressibility (solid fraction vs. compaction pressure), tabletability (tensile strength vs. compaction pressure), and compactibility (tensile strength vs. solid fraction) of four common direct compression excipients and a placebo formulation. The tabletability and compressibility of some of these materials were observed to be speed dependent whereas the compactibility of all materials tested was essentially independent of tableting speed. It is therefore proposed that the compactibility profile (tensile strength vs. solid fraction) is a predictor that is independent of tableting speed and can be used to predict tablet strength during formulation development and scale up.

Compressive Strength↗

PubMed2005

Quantifying errors in tableting data analysis using the Ryshkewitch equation due to inaccurate true density.

Although inaccurate true density affects analysis of powder compaction data, such effects have not been systematically evaluated in the literature. This work is aimed at quantitatively evaluating effects of inaccurate true density on tableting data analysis using the Ryshkewitch equation, sigma = sigma0 e - bepsilon, where epsilon is tablet porosity, sigma is tensile strength, sigma(0) and b are constants that are used to characterize tableting properties of a powder. Mathematical expressions are derived to enable reliable prediction of the influence of inaccurate true density on sigma(0) and b. The validity of the expressions is suggested by modeling the effects of inaccurate true density based on a set of accurate literature tableting data and confirmed using multiple sets of tableting data of water-containing powders that exhibit inaccurate helium pycnometry densities. Percentage errors in fitted sigma(0) and b as functions of errors in true density follow the derived mathematical expressions. With increasing percentage error in true density, percentage errors increase exponentially in fitted sigma(0) and increase linearly in fitted b, while R(2) is not affected. According to the mathematical expressions, true density with <0.28% error is required to achieve 4% accuracy in fitted sigma(0) for typical pharmaceutical powders.

Chemistry, Pharmaceutical↗

PubMed2005

True density of microcrystalline cellulose.

Microcrystalline cellulose (MCC) exhibits unusual tableting properties, sometimes, inconsistent with its high plasticity. It is found that some of the unusual tableting properties of MCC can be explained in part by the use of inaccurate true density during tableting data analysis. MCC true density as a function of water content is determined using a published method that can determine true density of water containing solids. Results suggest that literature MCC true densities tend to be overestimated as a result of limitations in helium pycnometry.

Cellulose↗

PubMed2004

A novel method for deriving true density of pharmaceutical solids including hydrates and water-containing powders.

True density is commonly measured using helium pycnometry. However, most water-containing powders, for example, hydrates, amorphous drugs and excipients, and most tablet formulations, release water when exposed to a dry helium atmosphere. Because released water brings significant errors to the measured true density and drying alters the nature of water-containing solids, the helium pycnometry is not suitable for those substances. To overcome this problem, a novel method has been developed to accurately calculate powder true density from compaction data. No drying treatment of powder samples is required. Consequently, the true density thus obtained is relevant to tableting characterization studies because no alteration to the solid is induced by drying. This method involves nonlinear regression of compaction pressure-tablet density data based on a modified Heckel equation. When true density values of water-free powders derived by this novel method were plotted against values measured using pycnometry, a regression line with slope close to unity and intercept close to zero was obtained. Thus, the validity of this method was supported. Using this new method, it was further demonstrated that helium pycnometry always overestimates true densities of water containing powders, for example, hydrates, microcrystalline cellulose (MCC), and tablet formulations. The calculated true densities of powders were the same for different particle shapes and sizes of each material. This further suggests that true density values calculated using this novel method are characteristic of given materials and independent of particulate properties.

Linear Models↗