Pharmaceutical Product Development and Supply, Janssen Research and Development, Johnson & Johnson, Beerse, Belgium.
Department of Chemical Sciences, SSPC the Science Foundation Ireland Research Centre for Pharmaceuticals, Bernal Institute, University of Limerick, Castletroy, Co. Limerick, Ireland.
Pharm Res. 2023 Jul;40(7):1709-1722. doi: 10.1007/s11095-022-03262-6. Epub 2022 Apr 22.
To investigate the difference in methods to determine the osmolality in solutions of stabilizers used for long-acting injectable suspensions.
The osmolality was measured by freezing point depression and vapor pressure for 11 different polymers and surfactants (PEG 3350, 4000, 6000, 8000, 20,000, PVP K12, K17 and K30, poloxamer 188, 388 and 407, HPMC E5, Na-CMC, polysorbate 20 and 80, vitamin E-TPGS, phospholipid, DOSS and SDS) in different concentrations.
Independently of the measuring method, an increase in osmolality with increasing concentration was observed for all polymers and surfactants, as would be expected due to the physicochemical origin of the osmolality. No correlation was found between the molecular weight of the polymers and the measured osmolality. The osmolality values were different for PVPs, PEGs, and Na-CMC using the two different measurement methods. The values obtained by the freezing point depression method tended to be similar or higher than the ones provided by vapor pressure, overall showing a significant difference in the osmolality measured by the two investigated methods.
For lower osmolality values (e.g. surfactants), the choice of the measuring method was not critical, both the freezing point depression and vapor pressure could be used. However, when the formulations contained higher concentrations of excipients and/or thermosensitive excipients, the data suggests that the vapor pressure method would be more suited.
研究用于长效注射混悬剂的稳定剂溶液中渗透压测定方法的差异。
通过冰点降低和蒸气压法测定了 11 种不同聚合物和表面活性剂（PEG3350、4000、6000、8000、20000、PVP K12、K17 和 K30、泊洛沙姆 188、388 和 407、HPMC E5、Na-CMC、聚山梨酯 20 和 80、维生素 E-TPGS、磷脂、DOSS 和 SDS）在不同浓度下的渗透压。
无论采用哪种测量方法，所有聚合物和表面活性剂的渗透压均随浓度的增加而增加，这是由于渗透压的物理化学性质所致。聚合物的分子量与测量的渗透压之间没有相关性。使用两种不同的测量方法，PVP、PEG 和 Na-CMC 的渗透压值不同。冰点降低法测定的渗透压值倾向于与蒸气压法提供的值相似或更高，总体上表明两种研究方法测量的渗透压值存在显著差异。
对于较低的渗透压值（例如表面活性剂），测量方法的选择并不关键，冰点降低和蒸气压法均可使用。然而，当制剂中含有较高浓度的赋形剂和/或热敏赋形剂时，数据表明蒸气压法更适用。
