Biopharmaceutics

Biopharmaceutics, in connection with pharmacokinetics, is the field that investigates and describes everything that happens with a medicinal product and the active substance between the moment of administration, the moment it exerts its action and the moment it is eliminated from the body. Biopharmaceutics connects the physico-chemical properties of an active substance and its dosage form, especially through the drug release characteristics, with its fate and action in the living organism. Actually biopharmaceutics describes how medicine formulation technologies can affect pharmacokinetics and pharmacodynamics. The route of administration, the way the active substance is released from the dosage form, and the way the body handles (absorbs, distributes, metabolises and excretes) the active substance, together determine its (duration of) action, its efficacy and the occurrence of adverse effects. This chapter explains general principles of biopharmaceutics and its relation to pharmacokinetics in the light of their implications on the design of medicines. It describes the general biopharmaceutical principles that are relevant to the major routes of administration: parenteral, oromucosal, oral, rectal, dermal, nasal, pulmonary and ocular. Topics discussed include solubility and dissolution, bioavailability, partition coefficient and pH partition theory, the biopharmaceutical classification system (BCS), excipient-, food-, drug- and herb-drug interactions, first-pass effects and drug metabolism, bioequivalence and new developments in the field of advanced drug delivery systems.</p

Biopharmaceutics

Biopharmaceutics, in connection with pharmacokinetics, is the field that investigates and describes everything that happens with a medicinal product and the active substance between the moment of administration, the moment it exerts its action and the moment it is eliminated from the body. Biopharmaceutics connects the physico-chemical properties of an active substance and its dosage form, especially through the drug release characteristics, with its fate and action in the living organism. Actually biopharmaceutics describes how medicine formulation technologies can affect pharmacokinetics and pharmacodynamics. The route of administration, the way the active substance is released from the dosage form, and the way the body handles (absorbs, distributes, metabolises and excretes) the active substance, together determine its (duration of) action, its efficacy and the occurrence of adverse effects. This chapter explains general principles of biopharmaceutics and its relation to pharmacokinetics in the light of their implications on the design of medicines. It describes the general biopharmaceutical principles that are relevant to the major routes of administration: parenteral, oromucosal, oral, rectal, dermal, nasal, pulmonary and ocular. Topics discussed include solubility and dissolution, bioavailability, partition coefficient and pH partition theory, the biopharmaceutical classification system (BCS), excipient-, food-, drug- and herb-drug interactions, first-pass effects and drug metabolism, bioequivalence and new developments in the field of advanced drug delivery systems.</p

An adaptable model for growth and/or shrinkage of droplets in the respiratory tract during inhalation of aqueous particles

AbstractThe site of deposition of pulmonary delivered aerosols is dependent on the aerosol׳s droplet size distribution, which may change during inhalation. The aim of this study was to develop a freely accessible and adaptable model that describes the growth (due to condensation) and shrinkage (due to evaporation) of inhaled droplets as a function of the distance from the airway wall during various inhalation conditions, for a laminar flow scenario. This was achieved by developing a model with which the evaporation of water from a droplet surface or condensation of water onto the droplet surface can be calculated. This model was then applied to a second model that describes the heat and mass transfer from the airway wall to the inhaled aerosol. The latter was based on the Weibel model. It was found that the growth and shrinkage of inhaled droplets markedly differs, depending on the distance from the airway wall. Droplets near the wall start to grow immediately due to fast water vapor transfer from the wall to the cold inhaled air. This growth continues until the air reaches body temperature and is fully saturated. However, droplets in the center of the airway first evaporate partly, due to a delay in water vapor transfer from the airway wall, before they start to grow. Depending on the conditions during inhalation, the droplet size distribution can widen considerably, which may affect the lung deposition and thereby the efficacy of the inhalation therapy. In conclusion, the model was able to show the effect of the conditions in the respiratory tract on the growth and shrinkage of inhaled droplets during standard inhalation conditions. Future developments can be aimed at expanding the model to include turbulent flow and hygroscopic growth, to improve the accuracy of the model and make it applicable to both droplets of solutions and dry particles

Model to predict inhomogeneous protein-sugar distribution in powders prepared by spray drying

AbstractA protein can be stabilized by spray drying an aqueous solution of the protein and a sugar, thereby incorporating the protein into a glassy sugar matrix. For optimal stability, the protein should be homogeneously distributed inside the sugar matrix. The aim of this study was to develop a model that can predict the distribution of protein and sugar in an evaporating droplet using bovine serum albumin (BSA) and trehalose as model protein and sugar, respectively. This was achieved by expanding a previously developed model that was able to predict the growth or shrinkage of inhaled droplets in the airways (Grasmeijer, Frijlink & Hinrichs, 2016). The droplet was considered to consist of a finite number of concentric spherical shells in which the change in concentration of components was calculated in time, enabling the prediction of concentration gradients inside the droplet. It was found that during evaporation of the droplet, an inhomogeneous protein–sugar distribution was formed even when surface active properties were not considered. The relatively large protein molecule was predicted to accumulate much faster at the surface of the droplet than the sugar due to slower diffusion, resulting in a lower sugar/protein ratio at the surface of the particle than in the center. For a mixture of BSA and trehalose, not considering surface active properties, it was predicted that 60% of protein was incorporated in the powder at a lower sugar/protein ratio than when protein and sugar would have been homogeneously distributed, which may hamper efficient protein stabilization. These predictions can be used to more accurately adapt the initial composition of the solution to ensure proper stabilization of the protein, for example by simply increasing the amount of sugar to increase the sugar/protein ratio at the surface. Or, if this is limited by the desired loading, changing the drying conditions to slow down the drying rate