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Monoclonal antibodies constitute nowadays an important therapeutic class and the number of approved molecules for clinical uses continues to increase, achieving considerable part of the therapeutic market. Yet, the stability in solution of these biopharmaceuticals is often low. That is why freeze-drying has been and remains the method of choice to obtain monoclonal antibodies in the solid state and to improve their stability. The design of freeze-drying process and its optimization are still topical subjects of interest and the pharmaceutical industry is regularly challenged by the requirements of quality, safety and efficiency set by the regulatory authorities. These requirements imply a deep understanding of each step of the freeze-drying process, developing techniques to control the critical parameters and to monitor the quality of the intermediate and the final product. In addition to quality issues, the optimization of the freeze-drying process in order to reduce the cycle length is of great interest since freeze-drying is known to be an energy-expensive and time-consuming process. In this review, we will present the recent literature dealing with the freeze-drying of monoclonal antibodies and focus on the process parameters and strategies used to improve the stability of these molecules and to optimize the FD process.

Most of biopharmaceuticals in clinical use today are available in a solution or suspension form and delivered by invasive routes (i.e. injection). However, several attempts have been made in order to develop effective oral formulations of 'biomolecules' characterized by a fragile structure and a low bioavailability. To achieve an efficient delivery of such molecules by non-parenteral route, in particular, via the oral route, novel concepts are needed not only to overcome significant enzymatic and diffusion barriers but also to ensure stability and biological activity. Vaccines and antibodies have a special interest as biomolecules because of their high therapeutic efficacy both in prevention and treatment of several chronic diseases. In this review, we would like to highlight the trends made in the development of pharmaceutical forms to deliver these molecules by the oral route. Hence, we will focus on the description of the different forms (solutions, suspensions, powders, tablets, micro and nanocarriers …) available today or under research study, in which product stability and efficacy are maintained. A special attention will be paid to the formulation strategies that may include the addition of several functional excipients and/or adjuvants, aiming to protect, to functionalize or to modulate their release in the body.

Polymorphic transformations that may occur during mechanical treatment are of great interest for the production of pharmaceutical solids. Anhydrous caffeine is a well-known example of such transformations but a careful reading of the already existing literature shows that published results are contradictory. In this study, both forms of caffeine, form I and form II, respectively metastable and stable at ambient pressure and temperature, were submitted to compression in an instrumented alternative press and to grinding, and were studied before and after treatment by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Compression experiments showed no changes of form II during compression, whereas form I was partially transformed into form II. Nevertheless, this transformation did not happen immediately. Form II appeared after a kinetically slow transformation and was clearly detectable only after a few days, fact that was never mentioned by previous authors. Same phenomenon was observed after the grinding of form I but also after an extensive grinding of form II. DSC and XRPD measurements indicated that polymorphic transformation did not happen directly, but that a new intermediate form was obtained after mechanical treatment, which slowly turned into form II within a few days.

Objective: The aim of this work is to study the effect of compaction on the specific surface area of tablets composed of various pharmaceutical materials (microcrystalline cellulose, lactose, and anhydrous calcium phosphate) compacted under seven degrees of compaction pressure., Methods: In a first part, the influence of the deformation behavior of the compacted materials on the evolution of the specific surface area is observed. In a second part, the brittle and ductile abilities of the materials are calculated using the specific surface area values. The experimental results are used to calculate the number and the force of interparticulate bonds inside the tablet., Results and Discussion: Tablets made of microcrystalline cellulose, which deform plastically, have specific surface areas that fall under pressure. In the case of lactose, the tablet specific surface area first increases to reach a maximum value at a pressure of 150 MPa. At higher pressure, however, the specific surface area decreases. The specific surface area of tablets composed of anhydrous calcium phosphate consistently increases, whatever the compaction pressure applied. Moreover, the evolution of the specific surface area is correlated with the tensile strength of the corresponding tablets. The number and the force of interparticulate bonds make it possible to classify the materials according to their deformation behavior and to quantify their ability to form cohesive tablets.

The influence of the composition and the relative humidity on the properties of pharmaceutical compacts prepared from mixtures of three excipients and three super-disintegrants was evaluated. Various amounts of super-disintegrant and different conditions of relative humidity during the storage were used to study mechanistically the disintegration process and to connect it to compact's mechanical properties. Three point single beam test was used to measure tensile strength and Young's modulus of compacts containing various amount of disintegrant and stored under various relative humidity. The presence of moisture within pharmaceutical compacts containing a disintegrant influences drastically their mechanical properties. Then, the results are related to micro-cracks visualized by MEB.