Buserelin nasal spray

The growth of testosterone-dependent tumors can be blocked by long-term administration of the three LH-RH analogs. The first therapeutic application of 32, 33, and 34 was in the treatment of prostate carcinomas. Buserelin came on the market as a nasal spray (Suprefact , 32) and leuprorelin (Carcinil , 33) as an injectable product in 1984. 

This luteinizing hormone-releasing hormone has been used in the treatment of endometriosis and hormone-dependent tumors. Modes of administration have included injections, nasal sprays and subcutaneous implantations. One study, conducted in pigs, demonstrated the value of glycodeoxycholate (a penetration enhancer) in improving the bioavailability of buserelin by up to five-fold after buccal delivery. ... 

An alternative to the pulmonary route of administration is the nasal route, which is less demanding when it comes to formulation. With regard to, for example, particle size and simpler device development (5,90), examples are Minirin (Ferring), desmopression, and Suprecur (Sanofi-Aventis), buserelin, which are proteins formulated as nasal drops or nasal spray, where bioavailabdities of approximately 3% to 10% can be obtained. The formulations are just protein dissolved in purified water containing preservatives chlorbutanol and benzalkonium chloride (91,92). However, more advanced delivery systems are also used, for example, chitosan formulations where bioavailabihties of 14% to 15% compared to subcutaneous administration can be obtained (90). A recent review by nium (2007) gives more details on nanoparticulate systems used for nasal delivery (93) or consult Costantino et al. (2007) on the physiochemical and therapeutic aspects (5). 

In preparations intended to obtain a systemic effect a spray solution is the favourite dosage form, because it enables accurate dosing. Examples of nasal preparations for systemic purpose are listed in Table 8.2. Examples of licensed preparations are nasal sprays with buserelin, fenta-nyl and vaccines (e.g. against airway infections) [8]. 

In medicines with intended systemic action a certain pH may be necessary to guarantee sufficient absorption of the active substance. In that case a buffer with high capacity is chosen, although it will have a negative effect on cilia. The more pH deviates from the physiological value, the more irritation will be felt. An example is a licensed nasal spray with the peptide buserelin in a citrate buffer (pH 5.5-6). Its Summary of product characteristics (SPC) says nasal irritation may occur, sometimes leading to epistaxis or hoarseness, as well as changes in taste and smell. 

When used correctly, nasal drops and sprays will not come into contact with the taste buds, but nevertheless they can give a sensation of taste [23]. This is easy to understand, as the olfactory organ plays an important role in the experience of taste. The clearance through the nasopharynx can be another cause, as a bitter taste is mainly observed at the rear of the tongue. Usually nasal preparations do not contain any flavouring agents. A side effect of especially nasal sprays may be a change in the users sensation of smell and taste. Examples are nasal sprays with fluticasone and with buserelin (Suprefact ). 

Commercially available peptide hormones delivered as nasal spray solutions include Synarel (nafare-lin), Stimate NS (desmopressin), Suprefact (buserelin acetate), and Miacalcin (salmon calcitonin). A list of current drugs in the market, doses, and bioavailability along with a comparative bioavailability profile for oral desmopressin is presented in Table 86.3. 

Buserelin acetate Injection 1 mg/mL, 100 gg metered nasal spray. 

Buserelin Injection 1 mg/mL, nasal spray 100 pg per metered dose. 

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