Modelling the effect of L/S ratio and granule moisture content on the compaction properties in continuous manufacturing

The pharmaceutical field is currently moving towards continuous manufacturing pursuing reduced waste, consistency, and automation. During continuous manufacturing, it is important to understand how both operating conditions and material properties throughout the process affect the final properties of the product to optimise and control production. In this study of a continuous wet granulation line, the liquid to solid ratio (L/S) and drying times were varied to investigate the effect of the final granule moisture content and the liquid to solid ratio on the properties of the granules during tabletting and the final tensile strength of the tablets. Both variables (L/S and granule moisture) affected the tablet tensile strength with the moisture content having a larger impact. Further analysis using a compaction model, showed that the compactability of the granules was largely unaffected by both L/S and moisture content while the compressibility was influenced by these variables, leading to a difference in the final tablet strength and porosity. The granule porosity was linked to the L/S ratio and used instead for the model fitting. The effect of moisture content and granule porosity was added to the model using a 3d plane relationship between the compressibility constant, the moisture content and porosity of the granules. The tablet tensile strength model, considering the effect of moisture and granule porosity, performed well averaging a root mean squared error across the different conditions of 0.17 MPa

Drying in a continuous wet granulation line: Investigation of different end of drying control methods

Continuous manufacturing in the pharmaceutical industry has been gaining traction in the past few years. To fully understand and optimise continuous manufacturing processes it is important not only to focus on the single units which act as building blocks but also to understand how the parameters in different units affect and interact each other and the final product. In this study, the drying behaviour of granules in a segmented fluidised bed dryer was studied. Granules were produced in a twin screw granulator, forming part of a continuous powder to table line (Consigma-25). The temperature readings and the moisture content were recorded during the drying process of granules produced with different amounts of liquid binder. From the temperature profiles, it was possible to create a method able to detect when the drying process loses efficiency (the drying rate drops) and therefore predict the optimal drying time at different conditions. The method was validated via online Near Infra Red (NIR) moisture measurements to detect the moisture content of the granules during the drying, and was compared to the available fixed drying time and temperature controlled end of drying methods. The method was successful in targeting a specific moisture content and could be used to locate the optimal drying temperature for a target moisture content in the future. The moisture content during the filling of the dryer was also recorded and provided further insight into the drying behaviour of the granules in the segmented dryer; this characteristic behaviour could later be used to detect problems during the filling time. The drying rate was also calculated making it possible to predict the optimal drying time at different operating conditions in the granulator and to assess the impact on drying of the different liquid to solid ratio used

Effects of Added Surfactant on Swelling and Molecular Transport in Drug-Loaded Tablets Based on Hydrophobically Modified Poly(acrylic acid)

A combination of NMR chemical shift imaging and self-diffusion experiments is shown to give a detailed molecular picture of the events that occur when tablets of hydrophobically modified poly(acrylic acid) loaded with a drug (griseofulvin) swell in water in the presence or absence of surfactant (sodium octylbenzenesulfonate). The hydrophobic substituents on the polymer bind and trap the surfactant molecules in mixed micelles, leading to a slow effective surfactant transport that occurs via a small fraction of individually dissolved surfactant molecules in the water domain. Because of the efficient binding of surfactant, the penetrating water is found to diffuse past the penetrating surfactant into the polymer matrix, pushing the surfactant front outward as the matrix swells. The added surfactant has little effect on the transport of drug because both undissolved solid drug and surfactant-solubilized drug function as reservoirs that essentially follow the polymer as it swells. However, the added surfactant nevertheless has a strong indirect effect on the release of griseofulvin, through the effect of the surfactant on the solubility and erosion of the polymer matrix. The surfactant effectively solubilizes the hydrophobically modified polymer, making it fully miscible with water, leading to a more pronounced swelling and a slower erosion of the polymer matrix

Development and Evaluation of Hydrophilic Colloid Matrix of Famotidine Tablets

The objective of the present study was to develop a once-daily sustained-release (SR) matrix tablet of famotidine. Nine different formulations (F1–F9) were prepared by direct compression method using Avicel PH101 as filler/binder in the range of 41–27% in F1–F3, 18–22% in F4–F7, and 16–18% in F8–F9 and hydroxypropyl methylcellulose (4,000 cps) as hydrophilic matrix was used in F1–F3 from 19% to 30%, around 40% in F4–F7, and 42–45% in F8–F9. Talc and Aerosil were added in the ratio of 0.7–1.2%. The tablets were subjected to various physical parameters including weight variation test, hardness, thickness, diameter, friability, and in vitro release studies. Assay was also performed according to the USP 30 NF 25 procedure. The results of the physical parameters and assay were found to be within the acceptable range. In vitro dissolution results indicated that formulation F4–F7, having around 40% of rate control polymer, produced a SR pattern throughout 24 h. F1–F3 showed drug release at a faster rate, while F8–F9 released much slower, i.e., <80% in 24 h. Model-dependent and model-independent methods were used for data analysis and the best results were observed for F4 in zero order (r2 = 0.984) and F6 in Korsmeyer and Higuchi (r2 = 0.992 and 0.988). The parameter n indicated anomalous diffusion, while β in Weibull showed a parabolic curve with higher initial slope. The f2 similarity test was performed taking F4 as a reference formulation. Only the F5–F7 formulations were similar to the reference formulation F4. The mean dissolution time was around 10 h for the successful formulation