Hello Ed4041,
There is very little information on time-released melatonin, other
than what I have found. I did find the answer to your timing wuestion,
however, and several possible time release methods.
?When to take: Depending on the severity of the sleep problem, take
time-released melatonin 1 to 3 hours prior to the time you usually
fall asleep. Since time release melatonin only lasts for 3 - 4 hours,
any need to shift sleep schedules more than 3 hours may require taking
another pill in 3 or 4 hours.?
http://www.talkaboutsleep.com/circadian-rhythm-disorders/circadian-rhythm-sleep-disorders/10-how-to-use-melatonin-correctly.htm
?Many companies manufacture melatonin. There are two kinds of
melatonin available, synthetic or natural. It is recommended to take
the synthetic time release formula. It is the closer to the molecular
make-up of melatonin and is made with pharmaceutical grade
ingredients. Natural melatonin may contain animal parts through which
viruses and diseases can be carried.? (The referenced page is no
longer available)
http://www.vanderbilt.edu/AnS/psychology/health_psychology/melatonin.htm
?Slow-release melatonin may not be as effective as standard (quick
release) formulations (20). If the dose is taken too early in the day,
it may actually result in excessive daytime sleepiness and greater
difficulty adapting to the destination time zone.?
http://216.239.51.104/search?q=cache:t2nrI_CsEb0J:www.mayoclinic.com/health/melatonin/NS_patient-melatonin+time+release+melatonin+%2B+how+long&hl=en&gl=us&ct=clnk&cd=14
?The fact that melatonin production declines so drastically with age
probably explains many of the sleep disturbances seen in the elderly.
Low doses of melatonin (0.3 mg) given as a supplement seem to be as
effective for inducing sleep as higher doses. But because the
half-life of melatonin is less than an hour, time-release supplements
of higher doses are more effective for sustaining sleep. Unlike sleep
induced by benzodiazepine drugs, melatonin-induced sleep does not
suppress Rapid Eye Movement (REM) sleep -- and does not result in
"hangover" feelings the next day [CLINICAL PHARMACOLOGY AND
THERAPEUTICS; Zhdanova,IV; 57(5):552-558 (1995)].?
?Night-time blood levels of melatonin peak at about 120 picograms per
milliliter just before the age of puberty. By age 30 blood levels have
fallen by half and by age 60 the levels of melatonin in the blood are
usually about 5 picograms per milliliter or less. The goal of
melatonin supplementation should be to restore youthful blood levels
of melatonin throughout most of the night with a time-release
medication. Melatonin should not be taken at daytime and high doses of
melatonin are strongly advised-against.
Because melatonin can cause drowsiness and is not very effective when
taken in daylight, one or two time-release capsules or tablets daily
at bedtime is preferable. Dosages in excess of 3 to 6 mg (milligrams)
should not be necessary, and often lower doses are preferred, and
equally effective for induction of sleep (if not the other benefits).?
http://www.benbest.com/nutrceut/melatonin.html
?Melatonin should only be taken at nighttime, usually about thirty
minutes prior to going to bed. If you are traveling on a long trip you
may want to take a dosage prior to getting on your flight and a higher
dosage pill prior to going to bed. If you commonly sleep during the
night, melatonin should not normally be taken during the day - and
vice versa - because melatonin plays a role in setting the body's
daily clock.
Does melatonin have that morning-after hangover effect of sleeping pills?
No. You should normally wake up well refreshed and full of energy. If
you wake up feeling a little tired you should reduce your dosage until
you wake up feeling well refreshed. You will not have the hangover
effect you may experience with over the counter or prescription
sleeping pills.?
http://www.melatonin.com/melatonin-faq.php#WHEN
?For children who continue to have a fragmented sleep pattern after an
initial two-week trial, consider using Sustained Release preparation.?
http://www.nhslothian.scot.nhs.uk/primarycarelibrary/2_ClinicalPractice/2_Guidelines/SCPs/eMelatonin.pdf
?Elderly patients using 2mg of controlled-release melatonin are much
more successful at weaning themselves off of medications such as
alprazolam, oxazepam, brotizolam, and lorzepam. In one study, 14 out
of 18 patients were able to completely discontinue their
benzodiazepine treatment after 4 to 6 weeks of melatonin therapy.?
?One double-blind study enrolled 320 people who were given 5mg of
standard melatonin, 5mg of slow-release melatonin, 0.5mg of standard
melatonin, or a placebo for 4 nights following plane travel. The
results showed improvements only with 5mg of standard melatonin.
Benefits were noted in time to fall asleep, quality of sleep, and
daytime drowsiness and fatigue. Positive results were seen in several
other studies but at least one study failed to find a significant
sleep-inducing effect for melatonin. On balance, the evidence is
strongly positive that melatonin can help sleep.?
?Sustained-release melatonin may provide sleep enhancement for those
who have difficulty remaining asleep. Several double-blind trials show
melatonin supplementation to be very effective in promoting sleep.
However, it appears that the sleep-promoting effects of melatonin
supplementation are most apparent if an individual's melatonin levels
are low. Melatonin supplementation does not act as a simple sedative
like a sleeping pill; only if this sleep-producing hormone is
deficient will supplementation be helpful. Furthermore, melatonin acts
to regulate or alter sleep rhythms, so its effect may be stronger with
problems getting to sleep initially than with sleep disturbances once
asleep.?
http://www.diagnose-me.com/treat/T77232.html
Formulation and release characteristics of hydroxypropyl
methylcellulose matrix tablet containing melatonin.
?A hydroxypropyl methylcellulose (HPMC) matrix tablet containing
melatonin (MT) was formulated as a function of HPMC viscosity, drug
loading, type and amount of disintegrant, lubricant and glidant, and
aqueous polymeric coating level and was compared with two commercial
products. The release characteristics of the HPMC matrix tablet were
investigated in the gastric fluid for 2 hr followed by study in
intestinal fluid. The surface morphology of an uncoated HPMC matrix
tablet using scanning electron microscopy (SEM) was crude, showing
aggregated particles and rough crystals or pores, but it became
smoother as the coating levels increased.?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10194604&dopt=Abstract
?BIOTEC CENTRE patented a double compartment transmucosal formulation
of melatonin with double action.
The claim is an immediate effect with fast release of melatonin and a
sustained release, simulating the night rates of melatonin, by the
transmucosal compartment. The tablet is mucoadhesive and can be kept
on site up to 10 hours. It has to be removed with the fingers when
wanted. No disturbances are observed 5 minutes after attachment. One
claim of this patent is to bring a rapid and clear signal for night in
correlation with plasma concentrations of melatonin. and to sustain
the effect for a long time (up to 10 hours, if wanted).
Melatonin was used as a model. But for this transmucosal
bicompartiment tablet, there are many other potential applications
with one or two active compounds in both compartments.?
http://www.biotec-dmpk-adme.com/patented-formulations.htm
?No statistically significant differences in objective sleep measures
were seen between baseline and treatment periods for the any of the 3
groups. Nonsignificant trends for increased nocturnal total sleep time
and decreased wake after sleep onset were observed in the melatonin
groups relative to placebo. Trends for a greater percentage of
subjects having more than a 30-minute increase in nocturnal total
sleep time in the 10-mg melatonin group and for a decline in the
day-night sleep ratio in the 2.5-mg sustained-release melatonin group,
compared to placebo, were also seen. On subjective measures, caregiver
ratings of sleep quality showed improvement in the 2.5-mg
sustained-release melatonin group relative to placebo. There were no
significant differences in the number or seriousness of adverse events
between the placebo and melatonin groups.?
http://adcs.ucsd.edu/t_Melatonin.htm
?Sustained-release melatonin may provide sleep enhancement for those
who have difficulty remaining asleep. Several double-blind trials show
melatonin supplementation to be very effective in promoting sleep.
However, it appears that the sleep-promoting effects of melatonin
supplementation are most apparent if an individual's melatonin levels
are low. Melatonin supplementation does not act as a simple sedative
like a sleeping pill; only if this sleep-producing hormone is
deficient will supplementation be helpful. Furthermore, melatonin acts
to regulate or alter sleep rhythms, so its effect may be stronger with
problems getting to sleep initially than with sleep disturbances once
asleep."
?This study aimed to explore the effects of melatonin on sleep, waking
up and well being in subjects with varying degrees of seasonal or
weather-associated changes in mood and behaviour. Fifty-eight healthy
adults exhibiting subsyndromal seasonal affective disorder (s-SAD)
and/or the negative or positive type of weather-associated syndrome
(WAS) were randomised to either 2 mg of sustained-release melatonin or
placebo tablets 1-2 h before a desired bedtime for 3 weeks. Outcome
measures were changes from baseline in sleep quality, sleepiness after
waking, atypical depressive symptoms and health-related quality of
life by week three. Early morning salivary melatonin concentrations
were measured at baseline and treatment cessation in all subjects.
Melatonin administration significantly improved the quality of sleep
(P=0.03) and vitality (P=0.02) in the subjects with s-SAD, but
attenuated the improvement of atypical symptoms and physical
parameters of quality of life compared to placebo in the subjects with
WAS, positive type.?
http://www.ktl.fi/portal/suomi/osastot/mielenterveys_ja_alkoholitutkimus/tutkimus/mielenterveys/epidemiologia_ja_genetiikka/mielialaa_saatelevat_tekijat/effect_of_controlled-release_melatonin_on_sleep_quality,_mood,_and_quality_of_life_in_subjects_with_seasonal_or_weather-associated_changes_in_mood_and_behaviour/
?The production of melatonin varies according to the amount of light
you're exposed to; for example, your body produces more melatonin in a
completely dark room than in a dimly lit one.
Melatonin supplements appear to be helpful for people whose natural
sleep cycle has been disturbed, such as travelers suffering from jet
lag. Melatonin may also be helpful in various other sleep disorders.
Melatonin is available in two forms: immediate-release (just plain
melatonin, also called "quick-release") and slow-release (a special
preparation, also called "controlled-release," designed to spread
melatonin absorption over many hours). It seems reasonable to suppose
that quick-release melatonin helps in falling asleep, while
slow-release melatonin helps in staying asleep, but study results are
inconsistent on this issue.?
http://healthlibrary.epnet.com/GetContent.aspx?token=8482e079-8512-47c2-960c-a403c77a5e4c&chunkiid=21811
?A total of 372 insomniac patients went on to receive the placebo for
2 weeks, followed by 2 mg of extended-release melatonin for 3 weeks,
taken every night between 9:00 and 11:00 pm.
Results of the questionnaire showed that, in general, melatonin
therapy improved the main symptoms of insomnia. Patients with lower
levels of melatonin production at baseline were linked to a higher
response to melatonin treatment in 3 of the 4 main areas: getting to
sleep, quality of sleep, and alertness and behavioral integrity
('getting things together') the next morning.
The insomniac patients were classified into 'low excreters' or 'high
excreters' of melatonin breakdown product, according to whether their
nighttime amount was below or above 3.5 micrograms. In the 112 low
excreters there were 58% responders to melatonin treatment, compared
with 47% in the 260 high excreters?
http://www.healthandage.com/default.cfm?curr_navi=02&curr_content=02&spr=en&framedef=1&curr_paramlist=healthandage;2903;2;haa_online_from;2;1;3;-;dsp_tooldetail
Delivery System ? Time release
==============================
This information applies to Contact Cold medicine, but the theory is similar:
?Contact has time release capsules which are coated with a material
that is resistant to stomach acid and takes a long time to dissolve so
the drug is released in the middle into the body. The dozens of
different little granules in a contact capsule are coated with
different thicknesses of this stuff so the drug inside is released at
different times from different nodules. This way your body receives a
continuous dose of the drug over a long period of time?
http://www.science.ca/askascientist/viewquestion.php?qID=362
?The first product close to market is a patent-protected 2 mg
prolonged-release melatonin formulation with the trade name Circadin?.
It mimics the body's physiological secretion profile of melatonin in
younger healthy adults. Neurim's database has shown that elderly
patients suffering from primary insomnia secrete significantly lower
levels of melatonin than healthy elderly with good sleep quality. Thus
the rationale for the use of Circadin? is to reconstitute the
decreased melatonin levels in this patient population. Consequently,
patients are able to improve the quality of their sleep and
subsequently improve day-time functioning. This physiological
treatment approach thus fundamentally differs from currently available
CNS-depressant hypnotics that act through the GABA-A receptor.?
http://www.neurim.com/research_port1.htm
?Now the miniaturization trend is reaching the pharmaceutical
industry. Thanks to advances in nanotechnology, drugs may soon be
presented in the form of a nanoparticulate?a nanometer-scale structure
that could enhance drug solubility and availability, as well as
improve the timing or location of its release inside the body. Thanks
to nanotechnology, pills will have less in common with the tinctures
and extracts of old, and behave as tiny medical devices in their own
right.?
http://www.memagazine.org/nanosept04/speciald/speciald.html
?Adis Comments: Neurim Pharmaceuticals in Israel is developing a
prolonged-release formulation of the antioxidant hormone melatonin
[Circadin(R)] for the potential treatment of antipsychotic-induced
tardive dyskinesia and primary insomnia in elderly patients.
Preclinical and clinical studies have shown a patent-protected
prolonged-release melatonin formulation to improve sleep quality in
elderly patients with insomnia; regulatory filing for the product for
primary insomnia in elderly patients has been submitted in Canada and
Europe by Neurim Pharmaceuticals.?
http://pt.wkhealth.com/pt/re/rdd/abstract.00126839-200304020-00012.htm;jsessionid=DZ9kxzuPPPVre6nfSrt73CxYza2qWPbLJUfbxmBiLnY0ISaOPPpM!2053693457!-949856144!9001!-1
?NanoCrystal? Technology
For poorly water-soluble compounds, Elan?s NanoCrystal technology can
enable formulation and improve compound activity and final product
characteristics. Fifty times smaller than conventional micronization,
NanoCrystal particles are produced by a proprietary milling technique
and stabilized against agglomeration to create a suspension that
behaves like a solution. A number of pharmaceutical products that
incorporate NanoCrystal technology have been successfully
commercialized.
Extended Release Technologies
An extended-release dosage form may be desirable to provide patients
with a convenient dosage regimen that allows less frequent dosing,
thus enhancing compliance. Extended release dosing can reduce
peak-related side effects, maintain therapeutic concentrations
throughout the dosing period avoiding periods of insufficient
therapeutic plasma concentrations between doses, and enable a less
frequent dosing regimen.
Delayed Release Technology
Chronotherapy is an example of where delayed release is desirable, as
in night-time dosing for an early morning effect. Delayed-release
products may also be formulated to protect an acid-labile drug from
the low pH in the stomach, or target the lower gastrointestinal tract
for local effect, thus minimizing systemic exposure and achieving a
target profile.
Pulsatile Release Technology
There are instances where a zero-order release profile is not ideal.
Profiles that do not exhibit zero-order release may be preferable in
certain circumstances, such as profiles where drug tolerance may
develop, the pharmacodynamic effect is dependent on a drug-free
interval, or varying plasma levels are required at different times of
the day. A real world example: Elan?s technology was applied to
Novartis? Ritalin® to produce a pulsatile once-daily dosage form,
which mimics the original twice-daily dosage regime.
With its unique offering of specialized technologies, Elan delivers
extensive scientific expertise to solve difficult drug delivery and
life cycle management challenges facing customers today - and in the
future.?
http://www.elan.com/EDT/drug_delivery/
It?s hard to say which time-release method melatonin manufactures use,
but I would guess it?s similar to the form that Contact uses ? thinner
and thicker coatings, that dissolve at different times. Then again, it
may be a proprietary method.
There you go. Any further information I found was simply repeating
what I already had.
If this is not the answer you were seeking, please request an Answer
Clarification, and allow me to respond, before you rate. I?ll be happy
to assist you further on this question, if possible, before you rate.
Regards, Crabcakes
Search Terms
============
sustained release + melatonin + formulation
Time release + melatonin
Drug delivery + timed release
Drug delivery + slow release
extended release delivery
Controlled delivery + drugs |
