Bioavailability of intranasal drug delivery system

Satish Balakrishna Bhise, Adhikrao Vyankatrao Yadav, Amelia Makrand Avachat, Rajkumar Malayandi

Abstract


Nasal drug delivery system offers lucrative way of drug delivery of both topical and systemic therapies. The high permeability, high vasculature and low enzymatic environment of nasal cavity are well suitable for systemic delivery of drug molecules via nose.The noninvasiveness and self administrative nature of nasal delivery also attracts the formulation scientists to deliver protein and peptide compounds. Despite of all the advantages of nasal drug delivery, the bioavailability of nasally administered products, especially for protein and peptide molecules, is affected by many barriers such as physiological barriers, physicochemical barriers, and formulation barriers. This review will focus on the various bioavailability barriers
in nasal drug delivery and the strategies to improve the bioavailability of nasal dosage forms.


Full Text:

PDF

References


Chein YW, Su KS, Chang SF. Nasal systemic drug delivery. 2nd ed. New

York: Dekker; 1989. p. 26.

Kissel T, Werner U. Nasal delivery of peptides: an in vitro cell culture

model for the investigation of transport and metabolism in human

nasal epithelium. J Control Rel 1998;53:195-203.

Talegonkar S, Mishra PR. Intranasal delivery: An approach to by pass

the blood brain barrier. Ind J Pharmacol 2004;36:140-7.

Kao HD. Enhanced delivery of L Dopa by the administration of its

prodrug via nasal route. Ph. D thesis, University of Kentucky Lexington,

Kentucky: 1995.

Wan Po AL, Rogers E, Shepphard M, Scott EM. Delivery system for non

parental vaccines. Adv Drug Del Rev 1995;18:101-9.

Bryant ML, Brown P, Gurevich N, McDougall IR. Comparison of the

clearance of radio-labelled nose drops and nasal spray as mucosally

delivered vaccine. Nucl Med Commun 1999;20:171-4.

Zuercher AW, Coffin SE, Thurnheer MC, Fundova P, Cebra JJ. Nasal-

associated lymphoid tissue is a mucosal inductive site for virus-specific

humoral and cellular immune responses. J Immunol 2002;168:1796-

Ugwoke MI, Verbeke N, Kinget R. The biopharmaceutical aspects of

nasal mucoadhesive drug delivery. J Pharm Pharmacol 2001;53:3-21.

Romeo VD, deMeireles JC, Gries WJ, Xia WJ, Sileno AP, Pimplaskar HK,

et al. Optimization of systemic nasal drug delivery with pharmaceutical

excipients. Adv Drug Deliv Rev 1998;29:117-33.

Michael H, Lisbeth I. Intra nasal insulin delivery and therapy. Adv Drug

Del Rev 1999;35:199-234.

Behl CR, Pimplaskar AP, Sileno JD, Romeo VD. Effect of physicochemical

and other factors on systemic nasal drug delivery. Adv Drug Deliv Rev

;29:89-116.

Kamath KR, Park K. Mucoadhesive preparation. New York: Marcel

Dekkar; 2003. p. 133-63.

O'Hagan DT, Critchley H, Farraj NF, Fisher AN, Johansen BR, Davis SS, etal. Nasal absorption enhancers for biosynthetic human growth hormone

in rats. Pharm Res 1990;7:772-6.

Ambruosi, A, Yamamoto H, Kreuter J. Body distribution of polysorbate-

and doxorubicin loaded [14C] poly(butyl cyanoacrylate) nanoparticles

after I.V. administration in rats. J Drug Target 2005;13:535-42.

Agu RU, Jorissen M, Willems T. Effects of pharmaceutical compounds

on ciliary beating in human nasal epithelial cells: A comparative study

of cell culture models. Pharm Res 1999;16:1380-5.

Charlton ST, Davis SS, Illum L. Evaluation of bioadhesive polymers as

delivery systems for nose-to-brain delivery: In vitro characterization.

J Control Rel 2006;61:167-82.

Martin M, Hutchinson LE, Hyde R, Peters GE. Analysis of structural

requirements for the absorption of drugs and macromolecules from

nasal cavity. J Pharm Sci 1987;76:535-40.

Hussain AA, Dakkuri A, Itoh S. Nasal absorption of ondansetron in rats:An alternative route of drug delivery. Cancer Chemother Pharmacol

;45:432-4.

Monterio-Riviere NA, Popp JA. Ultra structural characterization of the

nasal respiratory epithelium in rats. Am J Anat 1984;169:31-43.

Costantino HR, Illum L, Brandt G, Johnson PH, Quay SC. Quay Intranasal delivery: Physicochemical and therapeutic aspects. Int J Pharm

;337:1-24.

Verdugo P. Goblet cells secretion and mucogenesis. Annu Rev Physiol

;52:157-76.

Clary-Meinesz CF, Cosson J, Huitorel P, Blaive B. Temperature effect on

ciliary beat frequency of human nasal and tracheal ciliated cells. Biol

Cell 1992;76:335-8.

Wanner A. Clinical aspects of mucociliary transport. Am Rev Respir

Dis 1977;116:73-125.

Satir P, Sleigh MA. The physiology of cilia and mucociliary interactions.

Annu Rev Physiol 1990;52:137-55.

Zhou M, Donovan M. Recovery of nasal mucosa following laureth-9

induced damage. Int J Pharm 1996;130:93-102.

Illum L, Farraj N, Critvhley H, Davis SS. Nasal administration of

gentamycin using novel microsphere delivery system for drugs. Int J

Pharm 1988;46:261-5.

Marttin E, Nicolaas GM, Schipper J, Coos V, Frans WH. Nasal mucociliaryclearance as a factor in nasal drug delivery. Adv Drug Del Rev

;29:13-38.

Passali D, Bianchini Ciampoli M. Normal values of mucociliary transport

time in young subjects. Int J Pediatr Otorhinilaryngol 1985;9:151-6.

Hybbinette JC, Mercke U. Effect of parasympathomimetic agonists

and antagonists on mucociliar y activity. Acta Otolar yngol

;93:465-73.

Corssen G, Alien CR. Acetylcholine: Its significance in controlling

ciliary activity of human respiratory epithelium in vitro. J Appl Physiol

;14:901-4.

Lindberg S, Khan R, Runer T. The effect of formoterol, a long acting

beta (2) -adrenoreceptor agonist on mucociliary activity. Eur J Pharmacol

;285:275-80.

Hee J, Guilerm R. Discussion on smoke and mucociliary transport. Eur

J Respire Dis Suppl 1985;66:86-8.

Donovan MD, Zhou CS. Drug effects on in vivo nasal clearance in rats.

Int J Pharm 1995;116:77-86.

Deitmer T, Scheffler R. The effect of different preparations of

nasal decongestants on ciliary beat frequency in vitro. Rhinology

;31:151-3.

Kanthakumar K, Cundell DR, Johnson M, Wills PJ, Taylor GW, Cole PJ, et

al. Effect of salmeterol on human nasal epithelial cell ciliary beating:

Inhibition of ciliotoxin in pyocyanin. Br J Pharmacol 1994;112:493-8.

Joki S, Sano J, Nuutinen P. Effect of some preservative agents on rat

guinea pig tracheal human nasal ciliary beat frequency. Am J Rhinol

;10:181-6.

Batts AH, Marriott C, Martin GP, Bond DW. The effect of some

preservatives in nasal preparation on mucociliary clearance. J Pharm

Pharmacol 1989;41:156-9.

Batts AH, Marriott C, Martin GP, Wood CF, Bond SW. The effect of some

preservatives in nasal preparation on mucus and ciliary components of

mucociliary clearance. J Pharm Pharmacol 1990;42:145-51.

Batts AH, Marriott C, Martin GP, Bond DW, Greaves JL, Wilson CG. The

use of radio labeled saccharin solution to monitor the effect of the

preservative thiomersal benzalkonium chloride and EDTA on human

nasal clearance. J Pharm Pharmcol 1991;43:180-5.

Ainge G, Bowles JA, McCormick SG, Richards DH, Scales MD. Lack of

deleterious effect of corticosteroid sprays containing benzalkonium

chloride on nasal ciliated epithelium. In vivo results in laboratory

animals. Drug Invest 1994;8:127-33.

Hirai S, Yashiki T, Mima H. Mechanisms for the enhancement of the nasal

absorption of insulin by surfactants. Int J Pharm 1981;9:173-84.

Hermens WA, Hooymans PM, Verhoef JC, Merkus FW. Effect of

absorption enhancers on human nasal tissue ciliary movement in vivo.

Pharm Res 1990;7:144-6.

Donovan MD, Flynn GL, Amidon GL. The molecular weight dependence

of nasal absorption: The effect of absorption enhancers. Pharm Res

;7:808-15.

Hermens WA, Deurloo MJ, Romeijn SG, Verhoef JC, Merkus FW. Nasal

absorption of 17 ß oestradiol by dimethyl ß cyclodextrin in rabbits and

rats. Pharm Res 1990;7:500-3.

Schipper NG, Romeijn SG, Verhoef JC, Merkus FW. Nasal insulin

delivery with dimethyl beta cyclodextrin as an absorption enhancer

in rabbits: Powder more effective than liquid formulations. Pharm Res

;10:682-6.

Romeijn SG, Verhoef JC, Martin E, Merkus FW. The effect of nasal drug

formulations on ciliary beating in vitro. Int J Pharm 1996;135:137-45.

Okudu M, Mygind N. Pathophysiological basis for topical steroid

treatment in nose. 1st ed. London: Tindall; 1980. p. 23-33.

Liu CM, Okuda M. Injurious effect of eosinophil extract on the human

nasal mucosa. Rhinology 1988;26:121-32.

Mygind T, Lildhold T. Nasal Polyposis. An Inflammatory Disease and its

Treatment. 1st ed. Copenhagen: Munksgaard; 1997. p. 50-60.

Winther B, Brofeldt S, Grønborg H, Mygind N. Pathology of naturally

occurring colds. Eur J Respir Dis 1983;128:345-7.

Toft A, Wihl JA, Toxman J, Mygind N. Double-blind comparison between

beclomethasone dipropionate as aerosol and as powder in patients

with nasal polyposis. Clin Allergy 1982;12:391-401.

Brittebo EB. Metabolism of progesterone in the nasal mucosa in mice

and rats. Acta Pharmacol Toxicol 1982;51:441-5.

Hussain A, Hamadi S, Kagoshima M, Iseki K, Dittert L. Does increasing

the lipophilicity of peptides enhance their nasal absorption. J Pharm

Sci 1991;80:1180-1.

Hussain AA, Hirai S, Bawarshi RS. Nasal absorption of propranolol. J

Pharm Sci 1979;68:1196-9.

Bawarshi-Nassar RN, Hussain A, Crooks PA. Nasal absorption of 17a-

ethinyl estradiol in the rat. J Pharm Pharmacol 1989;41:214-5.

Huang CH, Kimura R, Bawarshi-Nassar R, Hussain A. Mechanism of

nasal absorption of drugs I: Physical chemical parameters influencing

the rate of in-situ nasal absorption of drugs in rats. J Pharm Sci

;74:608-11.

Faraj JA, Hussain A, Aramaki Y, Iseki K, Kagoshima M, Dittert LW.

Mechanism of nasal absorption of drugs III: Nasal absorption of leucine

enkephalin. J Pharm Sci 1990;79:768-70.

Pontiroli AE. Peptide hormones: Review of current and emerging uses

by nasal delivery. Adv Drug Deliv Rev 1998;29:81-7.

Prego C, Garcia M, Torres D, Alonso MJ. Transmucosal macromolecular

drug delivery. J Control Rel 2005;101:151-62.

van Den Berg MP, Verhoef JC, Romeijn SG, Merkus MW. Uptake of

estradiol or progesterone into the CSF following intranasal and

intravenous delivery in rats. Eur J Pharm Biopharm 2004;58:131-5.

Sayani AP, Chien YW. Systemic delivery of peptides and proteins across

absorptive mucosa. Crit Rev Ther Drug Carrier Syst 1996;13:85-184.

Potschka H, Fedrowitz M, Loscher W. P-glycoprotein and multi drug

resistance-associated protein are involved in the regulation of extra

cellular levels of the major antiepileptic drug carbamazepine in the

brain. Neuroreport 2001;12:3557-60.

Wioland MA, Fleury-Feith J, Corlieu P, Commo F, Monceaux G, Lacau-

St-Guily J, et al. CFTR, MDR1, and MRP1 immuno localization in

normal human nasal respiratory mucosa. J Histochem Cytochem

;48:1215-22.

Henriksson G, Norlander T, Zheng X, Stierna P, Westrin KM. Expression

of P-glycoprotein 170 in nasal mucosa may be increased with topical

steroids. Am J Rhinol 1997;11:317-21.

Graff CL, Pollack GM. P-glycoprotein attenuates brain uptake of

substrates after nasal instillation. Pharm Res 2003;20:1225-30.

Graff CL, Pollack GM. Functional evidence for P-glycoprotein at the

nose-brain barrier. Pharm Res 2005;22:86-93.

Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics

A Treatise. 1st ed. New Delhi: Vallabha prakasan; 1995. p. 34

Jones N. The nose and para nasal sinuses physiology and anatomy. Adv

Drug Deliv Rev 2001;51:5-19.

Fisher A, Brown K, Davis S, Parr G, Smith DA. The effect of molecular

size on the nasal absorption of water soluble compounds in the albino

rat. J Pharm Pharmacol 1987;39:357-62.

Maitani Y, Machida Y, Nagai T. Influence of molecular weight and charge

on dextran and DEAE dextran in rabbits. Int J Pharm 1989;40:23-7.

Irwin WJ, Dwivedi AK, Holbrook PA, Dey MJ. The effect of cyclodextrins

on the stability of peptides in nasal enzymatic systems. Pharm Res

;11:1698-703.

Fisher AN, Illium L, Davis SS, Schachut EH. Di iodo L tyrosine labeled

dextrans as molecular size markers of nasal absorption in the rats. J

Pharm Pharmacol 1992;44:550-4.

Donovan M, Flynn, Amidon G. Absorption of polyethylene glycols 600

through 2000: the molecular weight dependence of gastrointestinal

and nasal absorption. Pharm Res 1990;7:863-8.

Cecilia W. Nasal drug delivery - In vitro studies on factors influencing on

absorption. Ph. D thesis. Acta Universitatis, Uppasala. 2002. p. 12-4.

Illum L, Watts P, Fisher AN, Hinchcliffe M, Norbury H, Jabbal-Gill I, et al.

Intranasal delivery of morphine. J Pharmacol Exp Ther 2002;301:391-

Costantino HR, Sileno AP, Johnson PH. Pharmacokinetic attributes of

intranasal delivery: Case studies and new opportunities. Drug Deliv

;3:8-11.

Dahl R, Mygind N. Anatomy, physiology and function of the nasal cavities

in health and disease. Adv Drug Deliv Rev 1998;29:3-12.

Greiff L, Andersson M, Svensson J, Wollmer P, Lundin S, Persson CG.

Absorption across the nasal airway mucosa in house dust mite perennial

allergic rhinitis. Clin Physiol Funct Imaging 2002;22:55-7.

Frey WH, Liu J, Chen X, Thorne. Delivery of 125I-NGF to the brain via

the olfactory route. Drug Deliv 1997;4:87-92.

Ohwaki T, Ishii M, Aoki S, Tatsushi K, Kayano M. Effect of dose, pH and

osmolarity on nasal absorption of secretin in rats III: In vivo membrane

permeation test and determination of apparent partition coefficient of

secretin. Chem Pharm Bull (Tokyo) 1989;37:3359-62.

Ohwaki T, Ando H, Watanabe S, Miyake Y. Effect of dose pH, osmolarity

on nasal absorption of secretin In rats. J Pharm Sci 1985;74:550-2.

Corbo DC, Liu JC, Chein YW. Drug absorption through mucosal

membranes. Effect of mucosal route and penetrant hydrophilicity.

Pharm Res 1989;6:848-52.

Shao Z, Park GB, Krishnamurthy R, Mitra AK. The physicochemical

properties, plasma enzymatic hydrolysis and nasal absorption of

acyclovir 2’ ester prodrugs. Pharm Res 1994;11:237-42.

Vyas TK, Shahiwala A, Marathe S, Misra A. Intranasal drug delivery for

brain targeting. Curr Drug Deliv 2005;2:165-75.

Lerner EN, Van ZE, Stewart GR. Enhanced delivery of octreotide to

the brain via transnasal iontophoretic administration. J Drug Target

;12:273-80.

Vyas TK, Shahiwala A, Marathe S, Misra A. Intranasal drug delivery for

brain targeting. Curr Drug Deliv 2005;2:165-75.

Nagai T, Nishimoto Y, Nambu N, Suzuki Y, Sekine K. Powder dosage form of insulin for nasal administration. J Control Release 1984;1:15-22.

Hirai S, Yashika T, Matsuzawa T, Mima H. Absorption of drugs from the

nasal mucosa of rat. Int J Pharm 1981;7:317-25.

Streisand B, Zhang J, Niu S, McJames S, Natte R, Pace NL. Buccal

absorption of fentanyl is pH dependent in dogs. Anesthesiology

;82:759-64.

Huang C, Kimura R, Nassar RB, Hussain A. Mechanism of nasal absorption of drugs I: Physicochemical parameters influencing the rate of in-situ nasal absorption of drugs in rats. J Pharm Sci 1985;74:608-11.

Hussain A, Hamadi S, Kagoshima M, Iseki K, Dittert L. Does increasing

the lipophilicity of peptides enhance their nasal absorption. J Pharm

Sci 1991;80: 1180-1.

Brannon MD, Herron JM, Reidenberg P, Affrime MB. Lack of hypothalamic- pituitary-adrenal axis suppression with once-daily or twice-daily beclomethasone dipropionate aqueous nasal spray administered to patients with allergic rhinitis. Clin Ther 1995;17:637-47.

Clement P, Roovers MH, Francillon C, Dodion P. Dose ranging placebo

controlled study of cetrizine nasal spray in adults with perennial allergic

rhinitis. Allergy 1994;49:668-72.

Chiang R, Barnes R, Shoupe D, Lobo RA. Dose related changes in LH

bioactivity with intranasal GnRH agonist administration. Contraception

;32:347-57.

Ohwaki K, Ando H, Kakimoto F, Uesugi K, Watanabe S, Miyake Y, et

al. Effects of dose, pH, osmolarity on nasal absorption of secretin

in rats: Histological aspects of the nasal mucosa in relation to the

absorption variation due to the effects of pH and osmolarity. J Pharm

Sci 1987;76:695-8.

Ohwaki K, Ando H, Watanabe S, Miyake Y. Effects of dose, pH,

and osmolarity on nasal absorption of secretin in rats. J Pharm Sci

;74:550-2.

Gizurarson S, Bechgaard E. Intranasal administration of insulin to

humans. Diabetes Res Clin Prac 1991;12:71-84.

Hardy JC, Lee SW, Wilson CG. Intranasal drug delivery by spray and

drops. J Pharm Pharmacol 1985;37:294-7.

Illum L, Jorgensen H, Bisgaard H, Krogsgaard O, Rossing N. Bioadhesive microspheres as a potential nasal drug delivery system. Int J Pharm 1987;39:189-99.

Vidgren P, Vidgren M, Vainio P, Nuutinen J, Paronen P. Double-labelling

technique in the evaluation of nasal mucoadhesion of disodium

cromoglycate microspheres. Int J Pharm 1991;73:131-6.

Morimoto K, Morisaka K, Kamada A. Enhancement of nasal absorption

of insulin and calcitonin using polyacrylic acid gel. J Pharm Pharmacol

;37:134-6.

Watanabe Y, Mizufune Y, Utoguchi N, Endo K, Matsumoto M. Studies

of drug delivery systems for a therapeutic agent used in osteoporosis.

II. Enhanced absorption of elcatonin from nasal mucosa in rabbits. Biol

Pharm Bull 1998;21:1191-4.

Illum L, Fisher AN, Jabbal-Gill I, Davis SS. Bioadhesive starch microspheres and absorption enhancing agents act synergistically to enhance the nasal absorption of polypeptides. Int J Pharm 2001;222:109-19.

Hussain MA, Koval CA, Shenvi AB, Aungst BJ. Recovery of rat nasal

mucosa from the effects of aminopeptidase inhibitors. J Pharm Sci

;79:398-400.

Donnelly A, Kellaway IW, Taylor G, Gibson M. Absorption enhancers as tools to determine the route of nasal absorption of peptides. J Drug

Target 1998;5:121-7.

Hussain MA, Aungst BJ. Nasal absorption of leucine enkephalin in rats

and the effects of aminopeptidase inhibition as determined from the

percentage of the dose unabsorbed. Pharm Res 1992;9:1362-4.

Barlow D, Takashi S. The design of peptide analogues for improved

absorption. J Control Release 1994;29:283-91.

Hofstee BH. Specificity of esterase. II. Behavior of pancreatic esterase I and II toward a homologous series of N-fatty acid esters. J Biol Chem 1952;199:365-71.

Y.W. Chien. Transnasal Systemic Medications. 1st ed. New York: Elsevier Science Publishing Co. Inc; 1985. p. 100-6.

Chien YW. Novel Drug Delivery Systems. 1st ed. New York: Marcel

Dekker Inc; 1992. p. 229-68.

Merkus FW, Verhoef JC, Marttin E, Romeijn SG, van der Kuy PH, Hermens WA, et al. Cyclodextrins in nasal drug delivery. Adv Drug Deliv Rev 1999;36:41-57.

Schipper NG, Hermens WA, Romeijn SG, Ver-Schiphoef J, Merkus FW.

Nasal absorption of 17-b-estradiol and progesterone from a dimethyl-b-

cyclodextrin inclusion formulation in rats. Int J Pharm 1990;64:61-6.

Aungst BJ, Rogers NL. Site dependence of absorption-promoting actions of laureth-9, Na salicylate, Na2EDTA, and aprotinin on rectal, nasal, and buccal insulin delivery. Pharm Res 1988;5:305-8.

Merkus FW, Schipper NG, Hermens WA, Romeijn SG, Verhoef JC.

Absorption enhancers in nasal drug delivery: Efficacy and safety. J

Control Rel 1993;24:201-8.

Deurloo MJ, Hermens WA, Romeijn SG, Verhoef JC, Merkus FW.

Absorption enhancement of intra nasally administered insulin by

sodiumtaurodihydrofusidate (STDHF) in rabbits and rats. Pharm Res

;6:853-6.

Baldwin PA, Klingbeil CK, Grimm CJ, Longenecker JP. The effect of

sodium tauro-24,25-dihydrofusidate on the nasal absorption of human

growth hormone in three animal models. Pharm Res 1990;7:547-52.

Kissel T, Drewe J, Bantle S, Rummelt A, Beglinger C. Tolerability and

absorption enhancement of intranasally administered octreotide

by sodium taurodihydrofusidate in healthy subjects. Pharm Res

;9:52-7.

fisher AN, Farraj NF, Hagan DT. Effect of L-a-lysophosphatidylcholine

on the nasal absorption of human growth hormone in three animal

species. Int J Pharm 1991;74:147-56.

Laursen T, Ovesen P, Grandjean B, Jensen S, Jørgensen JO, Illum P, et al. Nasal absorption of growth hormone in normal subjects: Studies with

four different formulations. Ann Pharmacother 1994;28:845-8.

Agerholm C, Bastholm L, Johansen PB, Nielsen MH, Elling F. Epithelial

transport and bioavailability of intranasally administered human growth

hormone formulated with the absorption enhancers didecanoyl-

L-a-phosphatidylcholine and a-cyclodextrin in rabbits. J Pharm Sci

;83:1706-11.

Hasegawa H, Ichinohe T, Strong P, Watanabe I, Ito S, Tamura S, et al.

Protection against influenza virus infection by intranasal administration

of hemagglutinin vaccine with chitin microparticles as an adjuvant. J

Med Virol 2005;75:130-6.

Read RC, Naylor SC, Potter CW, Bond J, Jabbal-Gill I, Fisher A, et al.

Effective nasal influenza vaccine delivery using chitosan. Vaccine

;23:4367-74.

Prego C, Garcia M, Torres D, Alonso MJ. Transmucosal macromolecular

drug delivery. J Control Rel 2005;101:151-62.

Witschi C, Mrsny RJ. In vitro evaluation of microparticles and polymer

gels for use as nasal platforms for protein delivery. Pharm Res

;16:382-90.

Lee VH, Yamamoto A. Penetration and enzymatic barriers of peptide

and protein absorption. Adv Drug Del Rev 1990;4:171-207.

Huang CH, Kimura R, Nassar RB, Hussain A. Mechanism of nasal

absorption of drugs, I: Physicochemical parameters influencing

the rate of in situ nasal absorption of drugs in rats. J Pharm Sci

;74:608-11.

Rasmussen GJ, Bundgaard H. Prodrugs of peptides: 15. 4-Imidazolidinone

prodrug derivatives of enkephalins to prevent aminopeptidase-

catalyzed metabolism in plasma and absorptive mucosae. Int J Pharm

;76:113-22.

Beauchamp LM, Orr GF, DeMiranda P, Burnette T, Krenistsky TA.

Amino acid ester prodrugs of acyclovir. Antiviral Chem Chemother

;3:157-64.

Smart JD, Nicholls TJ, Green KL, Rogers DJ, Cook JD. Lectins in drug

delivery: a study of the acute local irritancy of the lectins from Solanum

tuberosum and Helix pomatia. Eur J Pharm Sci 1999;9:93-8.

Suzuki Y, Makino Y. Mucosal drug delivery using cellulose derivatives

as a functional polymer. J Control Release 1999;62:101-7.

Ikechukwu Ugwoke M, Sam E, Van Den Mooter G, Verbeke N, Kinget

R. Nasal mucoadhesive delivery systems of the antiparkinsonian drug,

apomorphine: Influence of drug-loading on in vitro and in vivo release

in rabbits. Int J Pharm 1999;181:125-38.

Ugwoke MI, Agu RU, Vanbilloen H, Baetens J, Augustijns P, Verbeke N,

et al. Scintigraphic evaluation in rabbits of nasal drug delivery systems

based on carbopol 971P and carboxymethylcellulose. J Control Release

;68:207-14.

Illum L, Farraj NF, Davis SS. Chitosan as a novel nasal delivery system

for peptide drugs. Pharm Res 1994;11:1186-9.

Kubota R, Komiyama T, Shimada H. Evaluation of the method for

nifedipine administration for a rapid onset of clinical effect: A clinical

study in normal volunteers. Yakugaku Zasshi 2001;121:355-64.

Newman SP, Steed KP, Hardy JG, Wilding IR, Hooper G, Sparrow RA. The

distribution of an intranasal insulin formulation in healthy volunteers:

Eåect of diåerent administration techniques. J Pharm Pharmacol

;46:657-60.

Park H, Robinson JR. Mechanism of mucoadhesion of poly(acrylic acid)

hydrogels. Pharm Res 1987;4:457-64.

Loftsson T, Gudmundsdottir H, Sigurjonsdottir JF, Sigurdsson

HH, Sigfússon SD, Másson M, et al. Cyclodextrin solubilization of

benzodiazepines: formulation of midazolam nasal spray. Int J Pharm

;212:29-40.

Petersen H, Kullberg A, Edsbacker S, Greiff L. Nasal retention of

budesonide and fluticasone in man: Formation of airway mucosal

budesonide-esters in vivo. Br J Clin Pharmacol 2001;51:159-63.

Vila A, Sanchez A, Tobío M, Calvo P, Alonso MJ. Design of biodegradable

particles for protein delivery. J Control Release 2002;78:15-24.

Dyer AM, Hinchcliffe M, Watts P, Castile J, Jabbal-Gill I, Nankervis R,

et al. Nasal delivery of insulin using novel chitosan based formulations:

A comparative study in two animal models between simple chitosan

formulations and chitosan nanoparticles. Pharm Res 2002;19:998-

Edman P, Bjork E, Ryden L. Microspheres as a nasal delivery system for

peptide drugs. J Control Release 1992;21:165-72.

Illum L, Farraj N, Fisher A. Hyaluronic acid ester microspheres as a nasal

delivery system for insulin. J Control Release 1994;29:133-41.

Koochaki PE. Nasal pharmaceutical composition in powder form.

European Patent Application EP 571671, 1993.

Ryden L, Edman P. Effect of polymers and microspheres on the nasal

absorption of insulin in rats. Int J Pharm 1992;83:1-10.

Critchley HS, Farraj D, Illum L. Nasal absorption of desmopressin in

rats and in sheep: Effect of bioadhesive microsphere delivery system.

J Pharm Pharmacol 1994;46:651-6.

Vivien N, Buri P, Balant L, Lacroix S. Nasal absorption of metoclopramide

administered to man. Eur J Pharm Biopharm 1994;40:228-31.

Illum L, Farraj NF, Davis SS, Johansen BR, Hagan DT. Investigation

of the nasal absorption of biosynthetic human growth hormone in

sheep-use of a bioadhesive microsphere delivery system. Int J Pharm

;63:207-11.

Ryden L, Edman P. Effect of polymers and microspheres on the nasal

absorption of insulin in rats. Int J Pharm 1992;83:1-10.

Chien YW, Chang SF. Intranasal drug delivery for systemic medications.

Crit Rev Ther Drug Carr Syst 1987;4:67-194.




DOI: http://dx.doi.org/10.22377/ajp.v2i4.203

Refbacks

  • There are currently no refbacks.