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| | Beclomethasone dipropionate Basic information |
| | Beclomethasone dipropionate Chemical Properties |
| Melting point | 117-120 C | | alpha | D +98.0° (c = 1.0 in dioxane) | | Boiling point | 613.3°C (rough estimate) | | density | 1.0766 (rough estimate) | | refractive index | 1.4429 (estimate) | | storage temp. | Sealed in dry,2-8°C | | solubility | Chloroform (Slightly), Dioxane (Slightly, Sonicated), Methanol (Slightly, Heated | | form | Solid | | pka | 13.02±0.70(Predicted) | | color | White | | λmax | 238nm(EtOH)(lit.) | | Merck | 14,1019 | | CAS DataBase Reference | 5534-09-8(CAS DataBase Reference) |
| | Beclomethasone dipropionate Usage And Synthesis |
| Chemical Properties | Light Yellow Solid | | Originator | Propaderm,Kyowa Hakko,Japan,1972 | | Uses | Anti-arrhythmia Agent, corticosteroids | | Uses | antiasthmatic, topical antiinflammatory | | Uses | Beclomethasone Dipropionate (Betamethasone Dipropionate EP Impurity E) is an antiallergic, antiasthmatic (inhalate). Anti-inflammatory (topical). | | Definition | ChEBI: A steroid ester comprising beclomethasone having propionyl groups at the 17- and 21-positions. | | Manufacturing Process | 6 grams of 6β-methyl-1,4-pregnadiene-11β,17α,21-triol-3,20-dione-21-acetate
is dissolved in a mixture of 35 ml of dimethylformamide and 6 ml of pyridine.
To the resulting solution is added 2.5 ml of methanesulfonyl chloride and the
reaction mixture maintained at 80°-85°C for about 1 hour. The resulting red
solution is cooled in an ice bath and treated successively with 55 ml of
methanol, 240 ml of 5% aqueous sodium bicarbonate and finally with 360 ml
of water. The resulting reaction mixture is then allowed to stand at room
temperature overnight after which the precipitated product is removed by
filtration, washed repeatedly with water and dried to a constant weight in air
at about 50°C to produce 6β-methyl-1,4,9(11)-pregnadiene-11α,21-diol-3,20-
dione-21-acetate.
Hydrolysis of the acetate ester with alkali, e.g., sodium methoxide in
methanol, affords the free alcohol, 16β-methyl-1,4,9(11)-pregnadiene-17α,21-
diol-3,20-dione. To a suspension of 3 grams of 6β-methyl-1,4,9(11)-
pregnadiene-17α,21-diol-3,20-dione-21-acetate 40 ml of acetone is added at
0°C with stirring 2 grams of N-chlorosuccinimide and then 7 ml of a perchloric
acid solution prepared by dissolving 0.548 ml of 70% perchloric acid in 33 ml
of water. The resulting reaction mixture is stirred at 0° for about 4 hours 45
minutes.
The excess of N-chlorosuccinimide is destroyed by the addition of about 15
drops of allyl alcohol and 180 ml of water is then added with stirring. This
mixture is held at 0°C for about one hour. The precipitated 16β-methyl-1,4-
pregnadiene-9α-chloro-11β,17α,21-triol-3,20-dione-21-acetate is recovered
filtration. A solution of 250 mg of the chlorohydrin in 5 ml of 0.25N perchloric
acid in methanol is stirred for about 18 hours at room temperature to produce
16β-methyl-9α-chloro-11β,17α,21-trihydroxy-1,4-pregnadiene-3,20-dione
which is recovered by adding water to the reaction mixture and allowing the
product to crystallize. Propionic anhydride is then used to convert this material
to the dipropionate. | | Brand name | Beclovent (GlaxoSmithKline);
Beconase (GlaxoSmithKline); Qvar (3M
Pharmaceuticals); Vanceril (Schering). | | Therapeutic Function | Topical antiinflammatory, Glucocorticoid | | Biological Functions | Beclomethasone dipropionate is used primarily as an inhalation aerosol therapy for asthma and rhinitis. A
breakthrough in the discovery of new inhalation corticosteroids with reduced risks from systemic absorption was
that the 17α-monopropionate ester of beclomethasone (17-BMP) was more active than BDP and
21-monopropionate (21-BMP) esters. Thus, BDP is a pro-drug that is rapidly metabolized by esterases in
the lung and other tissues to its more active metabolite, 17-BMP, which has 30 times greater affinity for the GR
than BDP and approximately 14 times dexamethasone (Table 33.5). | | General Description | Beclomethasonedipropionate (Beclovent, Beconase, Vanceril, Vancenase)(BDP) is rapidly converted in the lungs to beclomethasone17-monopropionate (17-BMP), the metabolite that providesthe bulk of the anti-inflammatory activity. The monopropionatealso has higher affinity for the GR than either thedipropionate or beclomethasone. The portion of BDP that isswallowed is rapidly hydrolyzed to 17-BMP, 21-BMP(which arises by a transesterification reaction from 17-BMP), and beclomethasone itself. Beclomethasone hasmuch less GC activity than the monopropionate. | | General Description | Beclomethasonedipropionate, 9-chloro-11β-hydroxy-16β-methyl-17,21-bis-(1-oxopropoxy)-pregna-1,4-diene-3,20-dione (Beconase,QVAR), is used in nasal sprays and aerosol formulations totreat allergic rhinitis and asthma. | | Biological Activity | beclomethasone dipropionate(bdp) is a topically active and anti-inflammatory corticosteroid used in treatment of asthma and rhinitis [1].beclomethasone dipropionate(bdp) is a topically active and anti-inflammatory corticosteroid used in treatment of asthma and rhinitis. in addition, beclomethasone dipropionate has been reported to be previously developed as aqueous nasal formulations for the treatment of allergic rhinitis. moreover, beclomethasone dipropionate has shown the availability in dry nasal aerosol formulations as chiorofluoro carbon metered-dose inhaler nasal sprays [1]. | | Clinical Use | Beclomethasone dipropionate is a lipophilic prodrug that, when inhaled, shows a systemic
bioavailability of approximately 20% of the administered dose. The 16β-methyl group decreases
mineralocorticoid activity, and the 9α-chloro group increases both the glucocorticoid and
mineralocorticoid activity, resulting in potent anti-inflammatory activity with little or no
salt-retaining effects. | | Side effects | The main adverse effects are headache, sinusitis, and pain.
Beclomethasone dipropionate is metabolized to the more active 17α-monopropionate derivative
during absorption from the lungs and then further metabolized to the free alcohol in the liver. | | Metabolism | The dipropionate also is metabolized to the inactive 21-monopropionate in the liver. Beclomethasone
dipropionate and its metabolites are mainly excreted in the feces, with less than 10% excreted in
the urine. | | references | [1] ratner ph1, melchior a, dunbar sa, tantry sk, dorinsky pm. pharmacokinetic profile of beclomethasone dipropionate hydrofluoroalkane after intranasal administration versus oral inhalation in healthy subjects: results of a single-dose, randomized, open-label, 3-period crossover study. clin ther. 2012 jun;34(6):1422-31. |
| | Beclomethasone dipropionate Preparation Products And Raw materials |
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