Transdermal Administration of Bromocriptine.

Abstract

Bromocriptine (BRC) is a semi-synthetic ergot alkaloid and it has been used for the treatment of diseases caused by hyperprolactinemia and for some neurological disorders as a dopamine agonist in clinics.1) BRC is mainly used for the inhibition of lactation, 2) treatment of menstrual disorders, 3) Parkinson disease, 4) breast tumours, 5) infertility 6) and brain tumours. 7)Bromocriptine is well absorbed through the GI tract but it has low bioavailability because of the hepatic first pass effect, but many patients have complained with GI side effects, headache and dizziness.4) The long acting injectable form of BRC has been developed 2) and it avoids the gastrointestinal side effects but it is expensive and cannot be self-administered.An alternative delivery route such as vaginal application of BRC has been reported. 8,9) Bromocriptine is well absorbed from vagina. Acartürk and Altug have studied the vaginal ring formulation of BRC with polydimethylsiloxane in vitro and in vivo in rabbits. 10,11) It was shown that the controlled release intravaginal ring containing BRC was found to be effective to decrease the plasma prolactin level in rabbits.BRC has also used for the treatment of Parkinson disease and the transdermal administration may be more useful than vaginal administration, being not gender limited. Transdermal delivery of drugs is also very convenient from the application point of view and it offers several advantages over the other routes of drug administration and termination of the drug input is possible in problematic cases. 12,13) Transdermal systems represent one of the most successful non-oral systemic drug delivery system. However, because of limitations of the technology, the physical, chemical nature of the compounds and also lack of the knowledge about penetration mechanisms, transdermal drug delivery is not suited to all drugs and it needs to be justified for the therapies.14)The penetration mechanisms, histopathological hazards of the enhancers and vehicles need to be clarified.The aim of this study was to investigate an alternative delivery route for BRC. Several topical BRC gel formulations were developed using Carbopol (C-934), Daichitosan (CH) and Gantrez-SP215 (G-SP215) and applied to rabbits. Commercially available BRC tablets (Parlodel ® ) were also given to rabbits orally and plasma levels were compared. Two different penetration enhancers, sodium taurocholate (ST) and ethoxydiglycol-Transcutol ® (TR) were also used to improve BRC penetration. Preparation of Gel Formulations For formation of the gel, CH or C-934 was dispersed in water then acetic acid or 0.01 N NaOH was added, respectively. BRC was dissolved in absolute ethanol and then mixed with the gel. TR or ST was added for the preparation of CH-ST or CH-TR gel. G-SP215 solution in ethanol was neutralised by triethanolamine and mixed with BRC solution in ethanol. Bromocriptine (BRC) has been mainly used for the inhibition of lactation, treatment of menstrual disorders, Parkinson disease, breast tumours, infertility and brain tumo...

Proniosomal gel-mediated transdermal delivery of bromocriptine:in vitroandex vivoevaluation

“…[19] Chitosan gel mediated delivery of BCT revealed the effectiveness of transdermal route as an alternate to oral delivery. [20] Literature suggests the application of transdermal delivery system to improve the therapeutic efficacy of BCT by avoiding hepatic metabolism and manitaining optimal plasma concentrations for a long period. [20] The present work was designed to investigate the feasibility of using proniosomal gel as transdermal vehicle for BCT.…”

“…[20] Literature suggests the application of transdermal delivery system to improve the therapeutic efficacy of BCT by avoiding hepatic metabolism and manitaining optimal plasma concentrations for a long period. [20] The present work was designed to investigate the feasibility of using proniosomal gel as transdermal vehicle for BCT. The influence of the various surfactants and cosurfactants was evaluated on the characteristics of proniosomes.…”

Optimised nanoformulation of bromocriptine for direct nose-to-brain delivery: biodistribution, pharmacokinetic and dopamine estimation by ultra-HPLC/mass spectrometry method

“…BRC is available in tablet and capsule dosage form (2.5 --20 mg/day, in divided doses), and these dosage forms exhibit low bioavailability (6%) due to extensive first-pass metabolism and non-targeted delivery results in side effects such as GI side effects, headache and dizziness [16]. The long-acting injectable form, transdermal and vaginal delivery route of BRC have been already reported [17].…”

Insights into direct nose to brain delivery: current status and future perspective

“…Reports on currently available dosage forms, that is, tablet (SicriptinÔ), indicated that it could not cross BBB and, after oral administration of BRC, it exhibits low or incomplete absorption and low bioavailability due to high metabolism in the liver (Vautier et al, 2006). A number of strategies such as drug delivery and drug targeting systems have been investigated for BRC to prevent drug degradation and loss so as to increase its bioavailability with high concentrations of BRC accumulated in the targeted area (Degim et al, 2003). Esposito and coworkers investigated nanolipidic carriers (NLC) of BRC for brain delivery.…”