Complexities related to the amorphous content of lactose carriers

Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and regulatory agencies believe that the levels of amorphous content should be controlled once there is a relationship with the final product performance. This is however not an easy task. The current paper elaborates on multiple challenges and complexities that are related to the control of the amorphous content in lactose. The definition and quantification methods of amorphous lactose are reviewed, as well as challenges related to thermodynamic instability. Additionally, current monographs and recent position papers considering this parameter are discussed to provide an overview of the regulatory landscape. Development of a control strategy is recommended, provided that the amorphous content at a specific moment in the process has shown to have an impact on the performance of the dry powder inhaler

Complexities related to the amorphous content of lactose carriers

Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and regulatory agencies believe that the levels of amorphous content should be controlled once there is a relationship with the final product performance. This is however not an easy task. The current paper elaborates on multiple challenges and complexities that are related to the control of the amorphous content in lactose. The definition and quantification methods of amorphous lactose are reviewed, as well as challenges related to thermodynamic instability. Additionally, current monographs and recent position papers considering this parameter are discussed to provide an overview of the regulatory landscape. Development of a control strategy is recommended, provided that the amorphous content at a specific moment in the process has shown to have an impact on the performance of the dry powder inhaler

Complexities related to the amorphous content of lactose carriers

Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and regulatory agencies believe that the levels of amorphous content should be controlled once there is a relationship with the final product performance. This is however not an easy task. The current paper elaborates on multiple challenges and complexities that are related to the control of the amorphous content in lactose. The definition and quantification methods of amorphous lactose are reviewed, as well as challenges related to thermodynamic instability. Additionally, current monographs and recent position papers considering this parameter are discussed to provide an overview of the regulatory landscape. Development of a control strategy is recommended, provided that the amorphous content at a specific moment in the process has shown to have an impact on the performance of the dry powder inhaler

The impact of material chemistry and morphology on attrition behavior of excipients during high shear blending

Particle breakage by attrition is unavoidable in some unit operations and can lead to uncontrolled behavior of materials during processing. The aim of this study is to clarify the impact of material properties on attrition behavior. For the first time, an integral study with varying morphologies and chemistries is performed to identify the key drivers that impact attrition during high shear blending. Based upon the observed changes in particle size distribution, it was concluded that dicalcium phosphate (DCP) was the most prone to attrition, followed by mannitol, lactose and microcrystalline cellulose (MCC). Granular particles were more sensitive to attrition than sieved and spherical particles. Changes in bulk density, flow function coefficient and tablet tensile strength were observed as the result of attrition. The magnitude and direction of change in these parameters was not only dependent on the amount of attrition, but also on the morphology and the material deformation properties

Smart Specification Setting for Dry Powder Inhalation Carriers

The specifications of excipients are important to pharmaceutical manufacturers to ensure that the final product can be manufactured robustly over the entire lifecycle of a drug product. Particle size specifications are key for dry powder inhalation excipients and they should be agreed between users and suppliers. The current paper evaluates two development strategies to set particle size specifications. It is shown that the application of quality-by-design principles to specification setting could result in broader specifications, while it guarantees that efficacy, safety and manufacturing of the medication is not affected. A multitude of reasons exist to keep specifications broader than the production capability range, including improved risk-mitigation and potentially reduced regulatory challenges during and after registration

Smart Specification Setting for Dry Powder Inhalation Carriers

The specifications of excipients are important to pharmaceutical manufacturers to ensure that the final product can be manufactured robustly over the entire lifecycle of a drug product. Particle size specifications are key for dry powder inhalation excipients and they should be agreed between users and suppliers. The current paper evaluates two development strategies to set particle size specifications. It is shown that the application of quality-by-design principles to specification setting could result in broader specifications, while it guarantees that efficacy, safety and manufacturing of the medication is not affected. A multitude of reasons exist to keep specifications broader than the production capability range, including improved risk-mitigation and potentially reduced regulatory challenges during and after registration

Smart Specification Setting for Dry Powder Inhalation Carriers

The specifications of excipients are important to pharmaceutical manufacturers to ensure that the final product can be manufactured robustly over the entire lifecycle of a drug product. Particle size specifications are key for dry powder inhalation excipients and they should be agreed between users and suppliers. The current paper evaluates two development strategies to set particle size specifications. It is shown that the application of quality-by-design principles to specification setting could result in broader specifications, while it guarantees that efficacy, safety and manufacturing of the medication is not affected. A multitude of reasons exist to keep specifications broader than the production capability range, including improved risk-mitigation and potentially reduced regulatory challenges during and after registration

The impact of lactose type on disintegration: An integral study on porosity and polymorphism

Besides factors such as disintegrant and lubricant, the raw material properties of filler excipients can have an impact on the disintegration behavior of a tablet. The current research aims to model the impact of lactose properties on disintegration time. For the first time, the impact of lactose polymorphism, tablet tensile strength, and pore structure parameters on disintegration were evaluated in one study. Six different lactose qualities were compacted into tablets of different solid fractions in a formulation with 5 %w/w diclofenac sodium, 1 %w/w magnesium stearate and 2 %w/w croscarmellose sodium. A linear model was built to identify which parameters impact the disintegration time, using as potential variables the polymorphic composition of the lactose, the porosity, pore size distribution and the tablet tensile strength. The model variables were derived from literature and calibrated with data. After optimization, the model shows a strong correlation (r2 = 0.982) between measured and predicted disintegration times. Among all investigated variables, the polymorphic composition of lactose, and the pore size distribution have been identified to affect tablet disintegration most. A higher concentration of lactose monohydrate in tablets leads to faster tablet disintegration, explained by the slower dissolution rate of lactose monohydrate compared to anhydrous and amorphous lactose. Tablet tensile strength was not identified as a direct driver for disintegration. Instead, the pore size distribution is a mutual driver for both tablet tensile strength and disintegration. The obtained insights provide guidance on the importance of quality attributes of filler binders for the prediction of tablet disintegration. This study can therefore be used as a starting point for quality-by-design formulation development and for the development of mechanistic models to predict tablet disintegration