Intranasal drug delivery system

Y. W. Chien and S. F. Chang. Intranasal drug delivery for systemic medications. Crit Rev Ther Drug Carrier Syst 4 67-194 (1987). 

Wermeling, D.P., J.L. Miller, and A.C. Rudy. 2002. Systemic intranasal drug delivery Concepts and applications. Drug Deliv Tech 2 56. 

Ugwoke, M. I., Exaud, S., Van Den Mooter, G., Verbeke, N., and Kinget, R. (1999), Bioavailability of apomorphine following intranasal administration of mucoadhesive drug delivery systems in rabbits, Eur. J. Pharm. Sci., 9,213-219. 

A typical example of this type of drug-delivery system is the development of a metered-dose nebulizer for the intranasal administration of a precision dose of luteinizing hormone-releasing hormone (LHRH) and... 

Alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems, including liposomes, cyclodextrins, and micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally [2]. 

Intranasal drug delivery This drug delivery provides fast and direct access to systemic circulation without first-pass metabolism. Administration is not easy especially with uncooperative children, but small volumes involved, rapidity of execution, feasibility at home has made it more attractive, particularly for no-needle approach to acute Illnesses. Aerosols with an appropriate device can avoid swallowing and is more precise in terms of dose. Drugs such as benzodiazepines, fentanyl, diamorphine, and ketamine have been used successfully via this route (90). 

Kumar, M. Misra, A. Babbar, A.K. Mishra, A.K. Mishra, P. Pathak, K. Intranasal nanoemulsion based brain targeting drug delivery system of risperidone. Int. J. Pharm. 2008, 358 (1-2), 285-291. 

Fazil, M., Hassan, M.Q., Baboota, S., Ah, J., 2015. Biodegradable intranasal nanoparticulate drug delivery system of risedronate sodium for osteoporosis. Drug Deliv. 25, 1—11. 

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]. 

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. 

Educating the Patient and Family If lypressin or desmopressin is to be used in the form of a nasal spray or is to be instilled intranasally usingthe nasal tube delivery system, the nurse demonstrates the technique of instillation (see Fhtient and Family Teaching Checklist Self-Adnrinistering Nasal Vasopressin). The nurse includes illustrated patient instructions with the drug and reviews them with the patient. If possible, the nurse lias the patient demonstrate the technique of administration. The nurse should discuss the need to take the drug only as directed by the primary health care provider. The patient should not increase the dosage (ie, the number or frequency of sprays) unless advised to do so by the primary health care provider. 

Desmopressin (the synthetic analog of vasopressin) acts by increasing water retention and urine concentration in the distal tubules of the kidney. This drug is administered intranasally (20-40 pg or one to two sprays) using a unit-dose, spray pump delivery system. The duration of action is 10 to 12 hours. The medication is expensive. 

Whether it is for the development of new package formats, such as for intranasal drug administration or transdermal patches, or for more traditional delivery systems, such as cycle packs, solutions, or aerosols, the need to educate employees involved in the processing is essential to the transfer program s success. Identifying and controlling process variables are necessary while experience is gained, and the process is optimized and validated. 

Alternate delivery systems are the focus of many laboratories throughout the world. The major routes selected are oral, pulmonary, intranasal, transdermal, vaginal, and others. Successful drug delivery discoveries are the result of interdisciplinary efforts of biochemists, chemists, engineers, physicists, pharmaceutical scientists, and clinical investigators. 

Some protein drugs have been administered intranasally [16], an approach that frequently leads to significant systemic bioavailability. Although the intranasal approach has been attempted for drug delivery to the brain, it has only... 

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. 

The hi-dose delivery system for our intransal ketamine product candidate provides non-invasive (i.e. needle-free) administration compared to IV or IM injections, via a rugged, simple to use device that can be patient-administered if necessary. Each disposable device delivers a total of 30 mg ketamine with well-characterized, predictable pharmacokinetics. This approach to delivering subanesthetic doses of ketamine may be particularly advantageous in emergency situations where convenience, speed of drug delivery/onset, and avoidance of accidental needle sticks in healthcare providers are desirable. In addition, our intranasal ketamine product candidate was formulated to minimize neurotoxicity, a question that has been raised regarding the differently formulated ketamine product currently approved for anesthesia. 

R. Nave, H. Schmitt, L. Popper, Faster absorption and higher systemic bioavailability of intranasal fentanyl spray compared to oral transmucosal fentanyl citrate in healthy subjects. Drug Delivery 20 (2013), p. 216-223. 

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