Absorption enhancers in nasal drug delivery: efficacy and safety

Merkus, F. W. H. M.; Schipper, Nicolaas; Hermens, W.A.J.J.; Romeijn, Stefan; Verhoef, J.

doi:10.1016/0168-3659(93)90179-9

Cited by 104 publications

(33 citation statements)

References 25 publications

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“…Org2766 without additives (P<0.05). (Baldwin et al, 1990;Fisher et al, 1991;Merkus et al, 1993). Similar differences were also obtained for the nasal absorption of insulin with DMPCD.…”

Section: Resultssupporting

confidence: 65%

Nasal administration of an ACTH(4–9) peptide analogue with dimethyl‐β‐cyclodextrin as an absorption enhancer: pharmacokinetics and dynamics

Schipper

Verhoef

Lannoy

et al. 1993

British J Pharmacology

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1 The systemic absorption and the neurotrophic effect of the metabolically stabilized ACTH (4-9) analogue, Org2766, were investigated following intranasal (i.n.) administration. 2 Without additives the nasal bioavailability of the peptide was in the order of 15 and 10% in rats and rabbits, respectively. The absorption could be improved by addition of a variety of absorption enhancers to the nasal preparation. The P-cyclodextrin derivative, dimethyl-p-cyclodextrin (DMPCD) at a concentration of 5% (w/v) improved the absorption in rats about 5 fold from 13 ± 4% (mean ± s.d.) for administration of the peptide alone to 65 ± 21%, and in rabbits 1 to 2 fold, from 10 ± 6% to 17 ± 8%.3 The increased permeability of the rat nasal mucosa for Org2766 caused by DMPCD in rats reversed substantially within 1 h. However, the nasal absorption had not yet completely returned to the level without enhancer. 4 S.c. administered Org2766 accelerated the functional recovery from peripheral nerve damage in rats.However, the peptide did not facilitate nerve repair following i.n. administration with DMPCD, in spite of the fact that Org2766 was well absorbed. I.v. injection of Org2766 was also ineffective.

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“…Org2766 without additives (P<0.05). (Baldwin et al, 1990;Fisher et al, 1991;Merkus et al, 1993). Similar differences were also obtained for the nasal absorption of insulin with DMPCD.…”

Section: Resultssupporting

confidence: 65%

Nasal administration of an ACTH(4–9) peptide analogue with dimethyl‐β‐cyclodextrin as an absorption enhancer: pharmacokinetics and dynamics

Schipper

Verhoef

Lannoy

et al. 1993

British J Pharmacology

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“…This problem was tackled by use of penetration enhancers from different classes like surfactants, bile acids, phospholipids, and cyclodextrins. But somehow they are associated with nasal mucosal toxicity when used for prolonged period during treatment, this should be considered in the chronic conditions (11). Literature reports the troubleshooting of low nasal permeability problem by different formulation strategies like microemulsion system for the drugs like clonazepam (12), insulin (13), and diazepam (14) in which there is significant improvement in absorption owing to lipophilic nature and low globule size of the microemulsion system (12).…”

Section: Carvedilol (Crv) (±)-1-(carbazol-4-yloxy)-3-[[2-(omethoxyphmentioning

confidence: 99%

Nanosuspension Based In Situ Gelling Nasal Spray of Carvedilol: Development, In Vitro and In Vivo Characterization

2012

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Abstract. The objective of the present investigation was to develop in situ gelling nasal spray formulation of carvedilol (CRV) nanosuspension to improve the bioavailability and therapeutic efficiency. Solvent precipitation-ultrasonication method was opted for the preparation of CRV nanosuspension which further incorporated into the in situ gelling polymer phase. Optimized formulation was extensively characterized for various physical parameters like in situ gelation, rheological properties and in vitro drug release. Formation of in situ gel upon contact with nasal fluid was conferred via the use of ion-activated gellan gum as carrier. In vivo studies in rabbits were performed comparing the nasal bioavailability of CRV after oral, nasal, and intravenous administration. Optimized CRV nanosuspension prepared by combination of poloxamer 407 and oleic acid showed good particle size [d (0.9); 0.19 μm], zeta potential (+10.2 mV) and polydispersity (span; 0.63). The formulation containing 0.5%w/v gellan gum demonstrated good gelation ability and desired sustained drug release over period of 12 h. In vivo pharmacokinetic study revealed that the absolute bioavailability of in situ nasal spray formulation (69.38%) was significantly increased as compared to orally administered CRV (25.96%) with mean residence time 8.65 h. Hence, such in situ gel system containing drug nanosuspension is a promising approach for the intranasal delivery in order to increase nasal mucosal permeability and in vivo residence time which altogether improves drug bioavailability.

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“…Intranasal administration may be a promising route of administration for compounds such as peptides that are expected to have low bioavailability when administered via the oral route [15,16]. An additional advantage for migraine treatment is that potential drug absorption problems due to nausea/vomiting and gastric stasis during a migraine attack are circumvented.…”

Section: Discussionmentioning

confidence: 99%

Multiple-dose pharmacokinetics of intranasally administered IS-159 in healthy subjects

Giersbergen¹,

Dingemanse²

2003

Eur. J. Drug Metab. Pharmacokinet.

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This study was designed to investigate the multiple-dose pharmacokinetics of a range of intransal doses of IS-159, a serotonin 1B/1D receptor agonist. Intranasal doses of 1, 2, 4 and 6 mg of IS-159 were administered twice at an interval of 4 hours to 17 healthy male and female subjects in a two-way crossover study. Plasma concentrations of IS-159 were determined from blood samples taken at regular intervals up to 24 hours after the first administration during both treatment periods. IS-159 was rapidly absorbed and eliminated with a t(max) of approximately 15 min and a t(1/2) of approximately 1.6 hours. With increasing dose, the exposure increased dose-proportionally, and IS-159 pharmacokinetics appear not to be influenced by gender and food intake. The results showed dose-proportional pharmacokinetics of IS-159 in the dose range tested and a low propensity for drug accumulation.

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Absorption enhancers in nasal drug delivery: efficacy and safety

Cited by 104 publications

References 25 publications

Nasal administration of an ACTH(4–9) peptide analogue with dimethyl‐β‐cyclodextrin as an absorption enhancer: pharmacokinetics and dynamics

Nasal administration of an ACTH(4–9) peptide analogue with dimethyl‐β‐cyclodextrin as an absorption enhancer: pharmacokinetics and dynamics

Nanosuspension Based In Situ Gelling Nasal Spray of Carvedilol: Development, In Vitro and In Vivo Characterization

Multiple-dose pharmacokinetics of intranasally administered IS-159 in healthy subjects

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