DITROPAN chloride Chemical name : benzeneacetic acid, ?-cyclohexyl-?-hydroxy-, 4-(diethylamino)-2-

DITROPAN
XL®

Oxybutynin
chloride

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Extended-release
Tablets, USP

Introduction

Oxybutynin
is used to treat symptoms of overactive bladder, such as frequent urination and
inability to control urination. This is due to oxybutynin is an anticholinergic
medication can reduce muscle spasms of the bladder and urinary tract.

Mechanism
of action of oxybutynin, it inhibits the action of acetylcholine
neurotransmitters on smooth muscle particularly the M1 and M2 receptors of the
bladder, detrusor activity.

The
dosage regimen of oxybutynin is one tablet 2 – 4 times per day. The plasma
half-life ranges from 2 – 3 hours. Therefore the more effective medication for
the treatment and convenient have been developed to reduce the frequency of
medication and potential of side effect, including to improve the
pharmacokinetics (constant concentration was maintained over 24 hours with once
daily dosage regimen), minimizing the fluctuations between peak and trough
concentrations. 

Ditropan XL® is
an extended release tablets, based on the osmotic controlled-release oral
delivery system (OROS). To maintained over 24 hours of plasma concentration. The
current Ditropan XL® extended-release tablets are
available as 5(Pale yellow, round, tablet), 10(Pink, round, tablet) and 15 mg (Gray,
round, tablet) tablets for oral use.

 

 

 

 

 

System Components and Performance

DITROPAN XL® uses osmotic
pressure to deliver oxybutynin chloride at a controlled rate over approximately
24 hours. The system consists of an osmotically active bilayer core, which is
surrounded by semi-transparent membranes. Bilayer cores consist of layers of
excipients and push layers. There are osmotically active components with
precision laser drill holes.

 

Pharmaceutical information

Drug Substance

Proper name                  : oxybutynin chloride

Chemical
name     : benzeneacetic acid,
?-cyclohexyl-?-hydroxy-, 4-(diethylamino)-2- butynyl ester hydrochloride, (±)-.
4-(Diethylamino)-2-butynyl (±)-?-phenylcyclohexaneglycolate hydrochloride.

Molecular formula         : C22H31NO3 .HCl

Molecular
mass    : 393.9

Structural formula         :

 

 

Solubility             : readily soluble in water and
acids, but relatively insoluble inalkalis.

Pharmacokinetic Profile

Alison M. Comer
and Karen L. Goa Adis International Limited, Auckland, New Zealand, Extended-Release
Oxybutynin show comparison of mean plasma concentrations of R-oxybutynin
following administration of extended-release oxybutynin 10 mg once daily or
immediate-release oxybutynin 5mg every 8 hours for 1 day in 23 healthy
volunteers.

A graph shows that
extended-release oxybutynin 10 mg once daily slowly release oxybutynin into the
bloodstream and show target concentration over approximately 24
hours. Concentration fluctuations in extended-release oxybutynin are smaller
than fluctuations in immediate-release oxybutynin 5 mg every 8 hours.

Composition

Drug layer

Composition

Function

Oxybutynin
HCL

Active
pharmaceutical ingredient

Polyethylene
oxide (MW. 200,000)

Osmopolymer

HPMC
(MW. 9,200)

Binder

Sodium
chloride

Osmogen

Magnesium
stearate

Lubricant

 

Push layer

Composition

Function

Polyethylene
oxide (MW. 7,500,000)

Osmopolymer

Sodium
chloride

Osmogen

Ferric oxide

Colorant

HPMC (MW. 11,200)

Binder

Butylated hydroxytoluene

Antioxidant/Lubricant

Magnesium stearate

Lubricant

Polysorbate 80

absorption
enhancer

 

Semipermeable membrane

Composition

Function

Cellulose acetate

Semi-permeable
membrane

Polyethylene glycol

Plasticizer

 

Finish Coat

Composition

Function

Titanium dioxide

Opacifying
agents

Polyethylene glycol

Plasticizer

Ferric oxide

Colorant

 

Printing ink

Composition

Function

Iron oxide

Colorant

Polyethylene glycol

Plasticizer

 

Manufacturing
process

 

The main processes can be divided
into following flow chart.

 

 

Reference

 

1.Comer AM, Goa KL. Extended-Release
Oxybutynin. Drugs & Aging. 2000;16(2):149-55.

2. Goldenberg MM.
An extended-release formulation of oxybutynin chloride for the treatment of
overactive urinary bladder. Clinical Therapeutics.21(4):634-42.

3. Gleason DM,
Susset J, White C, Munoz DR, Sand PK. Evaluation of a new once-daily
formulation of oxybutynin for the treatment of urinary urge incontinence11This
study was funded by the Alza Corporation on behalf of Crescendo Pharmaceuticals
Corporation, Palo Alto, California. Urology. 1999;54(3):420-3.

4. https://www.webmd.com/drugs/2/drug-16864/ditropan-xl-oral/details

5. US005674895A

6. US005912268A

7. US
20050287185A1