Nasal drug absorption optimization

The difficulty with HLB as an index of physicochemical properties is that it is not a unique value, as the data of Zaslavsky et al. (1) on the haemolytic activity of three alkyl mercaptan polyoxyethylene derivatives clearly show in Table 1. Nevertheless data on promotion of the absorption of drugs by series of nonionic surfactants, when plotted as a function of HLB do show patterns of behaviour which can assist in pin-pointing the necessary lipophilicity required for optimal biological activity. It is evident however, that structural specificity plays a part in interactions of nonionic surfactants with biomembranes as shown in Table 1. It is reasonable to assume that membranes with different lipophilicities will"require" surfactants of different HLB to achieve penetration and fluidization one of the difficulties in discerning this optimal value of HLB resides in the problems of analysis of data in the literature. For example, Hirai et al. (8 ) examined the effect of a large series of alkyl polyoxyethylene ethers (C4,C0, Cj2 and C 2 series) on the absorption of insulin through the nasal mucosa of rats. Some results are shown in Table II. 

Notwithstanding these factors, the physical characteristics of compounds for optimal intranasal absorption are the same as for other absorption routes. The drug must dissolve in the fluids of the nasal mucosa and must be sufficiently lipophilic to cross the membranes of the nasal epithelium. Nasal absorption is facilitated by the high permeability of small venules and capillaries associated with the nasal mucusa. 

As pointed out by Baluom and colleagues, absorption enhancers are efficient in small body cavities such as the nasal and the rectum [52], In the fed state, the issues of dilution during gastric mixing would probably obviate the possibility of interaction between the dispersed phase and the small intestine. Using a perfused rat model, the authors showed that a synchronized administration of an absorption enhancer (sodium decanoate) is required for optimal absorption of a poorly absorbed drug (cefazoline) and that levels of the enhancer need to be sustained rather than high. 

As an exemplification, a novel system called PecSys (PS), which is a pectin based drug delivery system, is developed to gel on mucosal surfaces when applied. These systems are currently focused in their application in intranasal delivery of drugs where it plays the role of optimizing the absorption of lipophilic drugs into the circulation. The PS based systems were commonly used for the intranasal formulations constituting opioid analgesics for the rapid pain relief The lead product that uses the PS system is NasalFent, which is a fentanyl nasal spray formulation [82]. 

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