Nasal preparations: Conventional and advanced pharmaceutical dosage forms

Abstract

Nasal dosage forms (nasal preparations) are traditionally used for local drug delivery, often for cold and flu symptoms' therapy. Apart from conventional dosage forms such as nasal drops, ointments and gels and aqueous nasal products, nasal sprays are even more frequently used, where the active pharmaceutical ingredient can, depending on its solubility, be formulated as a solution or suspension (liquid sprays), or as nasal powders, and the judicious choice of packing material, i.e. the applicator (delivery device) is stressed. When about to formulate nasal sprays, apart from the choice of appropriate excipients, one should take care about the pump/dozer characteristics, dose uniformity, particle size and size distribution in bulk (in nasal suspensions and powders), but also during the application (nasal aerosol), mode of content dispensing, weight loss (stability), possible content leakage… Besides the local effect, intranasal application is being immensely explored as a potential route of application for drugs with systemic therapeutic effect, especially for the delivery of peptide/protein biopharmaceuticals, and in that context options for maintaining their stability and achieving better bioavailability (above 30% of the resorbed dose) are being explored.

Nazalni preparati (preparati za nos) tradicionalno se koriste za primenu lekova koji treba da ispolje lokalni efekat, najčešće za simptomatsku terapiju prehlade i gripa. Pored klasičnih farmaceutskih oblika kao što su kapi za nos, masti i gelovi za nos i vode za nos, u terapiji se sve više koriste nazalni sprejovi, kod kojih lekovita supstanca, zavisno od rastvorljivosti, može biti formulisana kao rastvor ili suspenzija (tečni sprejovi), ili kao prašak za nos, a akcenat se stavlja na optimalan izbor ambalaže, odnosno aplikatora (uređaja za primenu/isporuku leka). Pri formulisanju nazalnih sprejeva, pored izbora odgovarajućih ekscipijenasa, posebno se vodi računa o karakteristikama pumpe/dozatora, uniformnosti/ujednačenosti doze, veličini i distribuciji čestica po veličini u bulk-u (kod suspenzija i praškova za nos), ali i tokom primene preparata (nazalni aerosol), načinu raspršivanja sadržaja, gubitku mase (stabilnost), mogućem curenju sadržaja... Pored lokalnog efekta intranazalna primena se intezivno istražuje kao mogući put primene lekova sa sistemskim terapijskim efektom, posebno za isporuku peptidnih/proteinskih biofarmaceutika, i u tom smislu, se istražuju opcije za očuvanje stabilnosti ovih lekova i postizanje što bolje biološke raspoloživosti (iznad 30% resorbovane doze).