Formulating monoclonal antibodies as powders for reconstitution at high concentration using spray-drying: Trehalose/amino acid combinations as reconstitution time reducing and stability improving formulations

Progress in spray-drying of protein pharmaceuticals: Literature analysis of trends in formulation and process attributes

“…It has been proposed that amino acids can fill "free volume holes" in amorphous formulations, improving stability [160] or in the case of charged hydrophilic amino acids by the formation of H-bonds. [23] However, amino acids also have shown other advantages, such as the improvement of particle aerosolization [161] and parental dosage reconstitution. [162] In other cases, amino acids can also act as anti-oxidants, avoiding the degradation of formulation components.…”

“…[36,162] Its superior stabilizing ability is proposed to be associated to its side chain ability to form H-bonds with proteins. [23] However, in aerosolisable formulations of IgG, arginine was not successful in maintaining long-term stability. [16] Additionally, it has also been shown that used alone and in combination with other excipients, arginine was able to stabilize b-galactosidase, [46] catalase, lysozyme, [71] IgG4, [32] BSA [112,113] as well as an attenuated measles [132] and influenza antigen vaccine.…”

“…[71] The use of histidine alone does not seem to offer sufficient stabilization of proteins after spray-drying. [23] Glycine is a hydrophilic neutral amino acid constituted by an aliphatic side chain. [159] Similarly to histidine, glycine seems to stabilize proteins when used with sugars [11,13,78] or other amino acids, [71] i.e.…”

“…arginine or histidine, but is less effective when used alone. [23] ExuberaV R used a combination of glycine and mannitol in its formulation.…”

“…In a recent study, it has been shown that the use of histidine buffer is more beneficial than lactate, when spray-drying an IgG mAb. [23] Studies on the use of buffering versus non-buffered solutions, have demonstrated that the former have a beneficial impact on the stability and retention of potency of vaccines for hepatitis B and measles. [118,132] Moreover, when spray-drying lysozyme in aqueous mixtures of ethanol, it was found that the use of PBS instead of non-buffered water improved the retention of enzymatic activity after spray-drying.…”