Lecture 13 - formulation of CNS treatments Flashcards
what are Classe sf psychiatric disorder ?
Hallucinations, delusion - absent in neurosis, present in psychosis
symptoms resemble normal personality - yes N, no P
treatment options: N: noninvasive possible, P:invasive often, necessary
what is the comaplaicne for benzodiazepines and assures?
Benzodiazepines:
- Dependence may occur after 4-6 weeks of treatment
- Weaning is not easy: decrease of dose by 1/8 every fortnight Withdrawal can take many months
Anti-depressants SSRI:
- Suicide risk: small supply should be given at any one time
- Use of full dose for 4-6 months after symptoms have subsided is essential to prevent relapse
- Non-compliance is frequent once the patient’s mood has improved
- Withdrawal over 2-4 weeks
what are compliance issues thought to be with schizophrenia condition?
Thought disorders, delusions, auditive hallucinations, paranoid delusions
Acutely psychotic patient: parenteral administration to a reluctant patient
- Compliance discouraged by weight gain (especially with clozapine), precipitates diabetes
- 75-85 % patients will eventually relapse
A minimum 5-year maintenance period is recommended
Paranoid delusional states (“carers as spies or tormentors”)
Patients not swallowing tablets
- Concentrated oral liquid forms help because they cannot be hidden in the mouth rather than swallowing them
- Syrup-base preparations can cause tooth decay and obesity in the long term
Oral dispersible forms are preferred
what are sublingual tablets?
Drug release in the mouth followed by systemic uptake of the drug
- Rapid systemic effect, without first-pass liver metabolism
- Sublingual tablets are placed under the tongue
-Ex: buprenorphine (addiction)
what are orodispersible tablets and advantages of them?
Disintegration of the tablet in the mouth within one min in the presence of saliva
Advantages:
- No difficulty for swallowing
- Improved compliance (no hiding tablets in the cheek pouch)
-Ex: risperidone (autism), aripiprazole (schizophrenia), mirtazapine (depression)
what are extended release tablets and descried the disintegration process.
Ex: methylphenidate (Concerta XL®, autism, ADHD)
- Trilayer capsule-shaped rigid tablet
- Use of the Osmotic release oral system (OROS) technology
In the morning:
Dissolution of the drug overcoat
Immediate release of 22 % of the dose within 1 h
1 h later:
- Permeation of water through the membrane into the tablet core
- Expansion of the osmotically active polymer excipients in the push compartment, acting as an osmotic pump
1 h later:
- Permeation of water through the membrane into the tablet core
- Expansion of the osmotically active polymer excipients in the push compartment, acting as an osmotic pump
- Regular release of the drug through the orifice
-Regular delivery of the drug for the rest of the morning
1 h later:
- Membrane: control of the rate at which water enters the tablet core, Control of drug delivery
In the afternoon:
- The push mechanism continues to expand
- Increase of the drug release rate from the system with time, due to the drug concentration gradient incorporated into the two drug layers of the tablet
what are adavantegs of extended release tablets
Efficacy for 12h
- No impact of food intake
- Overcoming of the difficulties of multiple daily dosing
describe extended release capsules
Ex: methylphenidate (Equasym XL®, ADHD),
Capsules containing 2 types of beads
Beads without release-control membrane (“Uncoated beads”):
30% of dose rapidly released
Beads with release-control membrane (“Coated beads”):
70% of dose continuously released
what are advantages of extended release capsules?
Efficacy for 8 h
- No impact of food intake
- Overcoming of the difficulties of multiple daily dosing (administered once in the day)
what are advantages and disadvantages of suspension ?
Advantages:
Drug absorption faster than with tablets or capsules
Convenient when the drug is not soluble in water and when non-aqueous solvent cannot be used
The insoluble solids act as a reservoir and continuously release the drug
Long-term efficacy
-Disadvantage:
- Risk of sedimentation
- Risk of inaccurate dosage (use of a spoon)
Ex: paroxetine (anxiety)
what are advantages and disadvantages of solutions/ syrups?
Advantages:
- Drug already dissolved
Absorption faster than solid dosage forms or
suspensions
- Masking of unpleasant taste of the drug (autism)
- Easy to adjust the dose for a child’s weight
- Disadvantages:
- Risk of deterioration faster than solid dosage forms
- Risk of inaccurate dosage (use of a spoon)
Ex: risperidone (autism), amisulpride, pericyazine (schizophrenia), diazepam, fluoxetine (anxiety), methadone (addiction)
to be suitable for transdermal drug delivery, what should the CNS drug be?
have a low molecular weight (less than 500 Da)
have an aqueous solubility higher than 1 mg/ml to be removed by the blood supply
be moderately lipophilic (logP between 1 and 5)
be effective at low dose (20 mg)
have a low melting point (MP < 250°C): the lower the melting point of the drug, the higher its solubility in the stratum corneum lipids
describe matrix tye transdermal patches
Matrix-type transdermal patch
Ex: Methylphenidate (Daytrana®, ADHD) :
- Application of the patch to the hip area 2 h before an effect is needed
- Removal of the patch 9 h after application
what are advantages of patches?
Slow release and long lasting effect
- Avoidance of hepatic first pass metabolism
- Can be removed easily and quickly in case of adverse reactions and in function of needs
- High patient compliance
One application per day (good compliance)
- Regular drug release for 9 hours
what are limitations of patches?
Limitations:
- No exposure to external heat sources: the rate and extent of
absorption would be significantly increased (can be higher than 2-fold)
Overdose of methylphenidate
- No exposure to water: can affect patch adherence
- Contact sensitization: erythema with more intense local reaction (edema, vesicles) that does not significantly improve within 48 hours
