Administration routes nasal

Desmopressin may be given orally, intranasally, SC, or IV. The oral dose must be determined for each individual patient and adjusted according to the patient s response to therapy. When the drug is administered nasally, a nasal tube is used for administration. The nasal tube delivery system comes with a flexible calibrated plastic tube called a rhinyle. The solution is drawn into the rhinyle. One end is inserted into the nostril and the patient (if condition allows) blows the other end to deposit solution deep into the nasal cavity. A nasal spray pump may also be used. Most adults require 0.2 mL daily in two divided doses to control diabetes insipidus. The drug may also be administered via the SC route or direct IV injection. 

In recent years, much of the research work in the pharmaceutical sciences was focused on the development of effective vehicle systems, such as micelles, microemulsions, and liposomes, for drugs that are critical with respect to bioavailability. Knowledge of this subject is a prerequisite to developing vehicle systems for special administration routes, such as dermal, transdermal, intravenous, and nasal. 

Figure 11.5 Ovulation induction by leuprorelin in diestrous rats after iv, sc, rectal, nasal, oral, and vaginal routes of administration. (Note nasal absorption may have been underestimated in this study, due to drainage of the test solution. For example, nasal bioavailability has been determined as 18.7% in rats, in a study in which the nasal cavity was closed at the orifice and outlet)...

FIGURE 15 (a) Nasal administration of 100 U of (A) enoxaparin, (B) dalteparin, or (C) UFH formulated with ( ) and without (O) 0.25% tetradecylmaltoside. Data represent mean + SEM, n = 3. Asterisks indicate results that are significantly different from those obtained with the drug formulated with saline, P < 0.05. (b) Administration of 100U of enoxaparin via the subcutaneous (A), intravenous ( ), and nasal (O) routes. Nasal administration was performed with a formulation that included 0.25% TDM. Data represent mean SEM, n = 3. (Reproduced from ref. 83 with permission of John Wiley Sons.)... 

However, demands for non-human tests are still there, and several challenges have been tried, based on cell culture models or animal models, for measuring protein release as an indicator of irritancy Finally, the systemic toxicity of additives is a common concern with any route of administration. The nasal absorption of the additives, as well as of the primary ingredients, should be carefully assessed. 

Pulmonary delivery of drugs is the administration route of choice in respiratory diseases such as chronic obstructive pulmonary disease and asthma. Different devices are available, including metered-dose inhalers, dry powder inhalers, and nebulizers, and nearly 80% of asthmatic patients worldwide use metered dose inhalers (1). Chlorofluorocarbons have been used as an aerosol propellant in metered-dose inhalers however, they deplete the ozone layer and are being replaced by more environment-friendly propellants, even though the contribution of aerosols of this type to the total global burden of chlorofluorocarbons is less than 0.5%. The first chloro-fluorocarbon-free metered-dose inhaler for asthma treatment was approved by the FDA in 1996 (2) and the European Union has set 2005 as a target date for the withdrawal of all chlorofluorocarbon-based inhalers (1). In the USA, prescriptions for chlorofluorocarbon-free medications rose from 16.4 million in 1996 to 33.8 million in 2000 (2). Most of the chlorofluorocarbon-free medications were steroids for nasal use (27.2 million). However, chlorofluorocarbon-containing medications stiU represented two-thirds of all prescriptions and increased from 63.0 to 67.6 million dispensed (2). 

Ondansetron (OND), a. S-hydroxytryptaminej receptor antagonist, has been used for prevention of nausea and vomiting associated with emetogenic cancer therapy. In view of the condition being treated, intravenous and oral dosage forms of OND may be inconvenient and/or unfeasible for specific patient populations. The nasal cavity can be a potential alternative route. A dose of 1 mg/kg OND (Zofran injection, 2 mg/mL) was administered to male Sprague-Dawley rats intravenously or intranasally. The peak plasma level of OND was attained within 10 min after application to the nasal mucosa of the rat. The plasma concentration-time profiles for nasal administration were comparable to those for intravenous injection, indicating complete absorption via the nasal route. The terminal elimination half-lives of the two routes of administration were also similar. The nasal administration route of OND was superior to the oral route (in humans, the oral absolute bioavailability is only 56% and the time to peak concentration is 1.0-2.Ih) and as effective as the intravenous route. 

When given snbcntaneonsly, sumatriptan reaches its peak plasma concentration in approximately 12 minutes. Following oral administration, peak plasma concentrations occur within 1 to 2 honrs. Bioavailabihty following the subcutaneous route of administration is approximately 97% after oral administration or nasal spray, bioavailability is only 14 to 17%. The elimination half-life is approximately 1 to 2 hours. Sumatriptan is metabolized predominant-ly by MAO-A, and its metabolites are excreted in the urine. 

As for a formulation using another administration route, Leitner et al. developed a nasal delivery system of hGH [194] based on the thiomer polycarbophil-cysteine (PCP-Cys) in combination with the permeation mediator glutathione (GSH). Microparticles were prepared by dissolving PCP-Cys/GSH/hGH (7.5 1 1.5), PCP/ hGH (8.5 1.5), and mannitol/hGH (8.5 1.5) in demineralized water, followed by lyophilization and micronization. PCP-Cys/GSH/hGH and PCP/hGH microparticles showed a comparable size distribution (80% in the range of 4.8 to 23 pm) and swelled to almost four fold size in phosphate-buffered saline. Both formulations exhibited almost identical sustained drug release prohles. The intranasal administration of the PCP-Cys/GSH/hGH microparticulate formulation resulted in a relative bioavailability of 8.11%, which represents a three fold and a 3.3-fold improvement compared with that of PCP/hGH microparticles and mannitol/hGH powder, respectively. The nasal microparticulate formulation based on PCP-Cys/ GSH/hGH might represent a promising novel tool for the systemic delivery of hGH. 

Usually, desmopressin is administered intranasally by use of sprays or drops. This administration route of desmopressin was considered to be more efficacious than the oral route, because bypassing the gastrointestinal tract increases the absolute bioavailability from less than 1% to approximately 5%. However, nasal application of desmopressin is accompanied by high intersubject and intrasubject variability in plasma pharmacokinetics [215]. Therefore, there have been several pharmaceutical research efforts to improve nasal delivery of desmopressin. 

The lack of activity after oral administration for most peptides and proteins resulted in the past besides parenteral application into the utilization of nonoral administration pathways, for example, nasal, buccal, rectal, vaginal, percutaneous, ocular, or pulmonary drug delivery [27]. Drug delivery via these administration routes, however, is also frequently accompanied by presystemic degradation processes. Bioavailability of numerous peptides and proteins is, for example, markedly reduced after subcutaneous or intramuscular administration compared to their intravenous administration. The pharma-cokinetically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption... 

Klinguer, C., Beck, A., De-Lys, P., Bussat, M.C., Blaecke, A., Derouet, F., Bormefoy, J.Y., Nguyen, T., Corvai a, N. and Velin, D., 2001, Lipophilic quaternary ammonium salt acts as mucosal adjuvant when co-administrated by nasal route with antigens. Vaccine 19 4236-4244. 

The system can be used for various administration routes, including oral, nasal, parenteral, intra-ocular etc. 

Pharmacokinetics - labeling of a potential drug candidate. This study includes distribution studies of drug passage over the blood-brain barrier and selective accumulation in critical organs. Apart from intravenous administration, oral and nasal administration routes are other important applications employed for quantification of the deposition and disposition of a drug formulation. 

Section 16.2.6 discusses biopharmaceutics of nasal preparations fi om a general biopharmaceutics viewpoint. This subsection adds some more specific details, first on the nasal absorption and then on the many investigations on absorption enhancing substances. The interest for nasal absorption is predominantly raised by the desire to find an alternative administration route for systemically acting active substances. 

The nasal administration was shown to be an effective administration route for lipophilic active substances like fentanyl. Moreover, the nasal route has also been used for the systemic administration of small peptides like buserelin acetate, nafarelin acetate and desmopressin, aU of them containing ten or less amino acid residues. However, for these molecules the nasal route forms only a poor non-invasive alternative to injection, since the nasal bioavailability of these peptides is less than 3-5 %. 

In the request for a pharmacy preparation, the physician often prescribes the administration route. Pharmacists have to critically evaluate whether the proposed route is appropriate to reach the desired bioavailability. For example, conventional oral medications may not be suitable for patients with a nasogastric feeding tube, children, or nauseous patients and alternative routes such as parenteral, rectal, or nasal have to be considered (see also Sect. 37.6.3). When adapting a dosage form or administration route to special needs of a patient, the pharmacist is required to consider safety aspects. It is important to recognise that an active substance approved for oral administration may never have... 

As excipients, CDs have been widely used to cover the bitter taste of drugs, to increase their dissolution rates, to reduce irritation reactions and in low concentrations to suppress the haemolysis induced by some drugs [180]. Great effort has been made to develop CD-based drug formulations with different administrative routes, including parenteral, oral, pulmonary, nasal [181], transdermal, rectal [182] and ophthalmic [183] drug delivery [184]. 

Spray-freeze-dried products can be delivered to the human body by various routes of administration. Pulmonary, nasal and ophthalmic delivery, needle-free injection and sustained release injectables have been described in literature for SFD products [2]. For each route of delivery, different particle characteristics are essential. 

The intranasal formulation is the preferred route of administration owing to ease of administration and fewer adverse effects, which mainly are local in nature. Adverse effects associated with the intranasal formulation include rhinitis, nasal irritation, and dryness. Hypersensitivity can develop with either formulation and should be considered before administering to patients with a suspected risk of hypersensitivity. 

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