pharmaceutics exam 2 according to exam prep. sheet Flashcards
hard gelatin capsules
what is it made of
what does it consist of
how is it intended to be used?
what part of hard capsules is soluble in water
what part of hard capsules can be digested and absorbed
what happens when Gelatin is dissolved
how are most gelatins colored?
how is gelatin obtained?
what is the difference between gelatin in air vs when moist?
how much moisture do hard capsules contain?
how is the size of hard capsules determined
sizes of capsules
how many pharmacists compound capsules?
how do pharmacists fill hard capsules?
- used to make most capsules
- the capsule is made of:
gelatin, sugar & water - they are clear, colorless and tasteless
what it consists of
- has a long base or body with a small diameter
- cap to slide over the base
intended to be
- swallowed whole
- contents should be opened and administered in food or liquid with the acceptance of a pharmacist
- the gelatin is soluble in hot water & in warm gastric fluids
- gelatin is digested by proteolytic enzymes and absorbed
- When gelatin dissolves it exposes its medicinal contents to the gastric (or intestinal) bodily fluids
- Most are colored with FD&C and D&C dyes and made opaque by adding titanium dioxide.
Gelatin is obtained by the partial hydrolysis of collagen obtained from
- skin,
- white connective tissue, and
- bones of animals
- While stable in air, gelatin is subject to microbial decomposition when moist
- Hard capsules: contain between 13-16% moisture, but poor storage conditions can increase this level. Not good!
- size is determined by how much material will go inside
- sizes: 000 (largest) to 5 (smallest), 8 actual sizes [000,00,0,1,2,3,4 and 5]
- A pharmacist may compound capsules of a single medicinal agent, or combination of agents at the precise dosage prescribed for the patient
pharmacists use the punch method to fill capsules:
- Start with the exact number of capsules to be filled
- Powder to be encapsulated and placed on a sheet of paper, clean glass, or porcelain plate
- Using a spatula powder is formed into a cake
- Empty capsule body is held between the thumb and forefinger and “punched” vertically into the powder cake repeatedly until filled
soft gelatin capsules
how do they look/are they elegant?
what are they prepared to contain? what kind of liquids cannot be in soft capsules?
when should soft capsules not be used?
what preservatives are used to retard microbial growth
- they are pharmaceutically elegant and easily swallowed
Prepared to contain liquid, paste & dry fills
– Liquids that can easily migrate through the capsule shell cannot be encapsulated into soft gelatin capsules– so if the liquid can easily move through the shell, then it cannot be used
When not to be used?:
– When water content is > 5%
– When low molecular weight water-soluble and organic compounds are employed such as
* alcohols, ketones, amines, and esters.
Preservatives such as methylparaben and/or
propylparaben is used to retard microbial growth – these are antifungal
capsule size
how is the size determine
what are the size ranges for humans
how many sizes are there for capsules
how can pharmacists utilize the sizes?
- the size is always determined by the amount of material to be incorporated
- For human use: 000 (the largest) to 5 (the smallest) are commercially available.
- There are 8 actual sizes [000,00,0,1,2,3,4 and 5]
* Numerical designations are arbitrary, and do not indicate the capsule’s capacity - A pharmacist may compound capsules of a single medicinal agent, or combination of agents at the precise dosage prescribed for the patient
preparation & filling
if things are to be added to preparations to facilitate manufacturing, what must be be
what are the two types of ways to fill capsules?
what must you keep in mind when cleaning and polishing capsules?
they must be:
– Harmless (in the quantities used)
– Do not exceed the minimum amounts required to provide their intended effect
– Do not impair the bioavailability of the product
– Do not interfere with assays to evaluate dosage form
method 1 to fill capsule: torbial torsion scale
- Formulation must be weighed directly to the capsule. It wouldn’t be accurate otherwise.
- To compensate for the weight of the empty capsule being filled, the same capsule must be placed on the other side of the balance with a weight equal to the amount to be filled
method 2: punch method
Pharmacists use the “punch” method
– Start with the exact number of capsules to be
filled
– Powder to be encapsulated and placed on a sheet of paper, clean glass, or porcelain plate
– Using a spatula powder is formed into a cake
An empty capsule body is held between the thumb and forefinger and “punched” vertically into the powder cake repeatedly until filled.
when cleaning and polishing capsules:
- Small amounts of powder may adhere to the outside of capsules after filling
cleaning & polishing
- what may adhere on the outside of the capsule
what must you do before packaging and dispensing and how do you do it
for large-scale cleaning, what can remove extraneous materials?
Small amounts of powder may adhere to the outside of capsules after filling
- Must remove before packaging and dispensing, wipe with clean gauze or cloth
- On large-scale cleaning, a vacuum can remove extraneous materials
compendial requirements
Things added to preparations to facilitate their manufacture can only be used if?
– Harmless (in the quantities used)
– Do not exceed the minimum amounts required to provide their intended effect
– Do not impair the bioavailability of the product
– Do not interfere with assays to evaluate dosage form
inspecting, counting, storage, and handling
are capsules or tablets easier to store and transport
inspecting
counting:
handling:
capsules are Easier storage and transport
influences of food on gastric emptying
for light and heavy objects, do they float or sink
- the more food in your stomach, the longer it takes for gastric emptying to occur and for the capsule to be absorbed
light objects float on gastric contents
heavy objects fall to the base of greater curvature
different types of tablets
are tablets all the same size
why are there smooth tablets
C
M
S
F
G
E
B
I
E
V
- Often vary in size,
shape, hardness, thickness, and in their ability to dissolve In fluids. - These tablets are grooved
- Are therefore intended
to be broken into two parts.
- Why? Offers flexibility - Patients can swallow
them easily or use in divided
doses
Compressed tablets (C.T.):
Usually contain the following in addition to medicinal agents
* Diluents or Fillers: Add bulk to prepare a certain size
* Binder or Adhesives: Promote adhesion of the particles
of the formulation
* Disintegrants: Promotes breakup of tablets/drug availability
* Antiadherents/ glidants/ or lubricating agents
* Miscellaneous Adjuncts: Colorants and flavorants to
enhance overall appearance
- Multiple compressed tablets (M.C.T.):
More than a single compression - Produces multiple-layered tablet or a tablet within a tablet
- Each layer may contain diff. medicinal agents. Why? * Separation may be required to avoid chemical and
physical incompatibility - Staged drug release
- General appearance of multiple-layered tablet
- Sugar-coated tablets (S.C.T):
Compressed tablet can be covered with a colored or an uncolored sugar layer
– The coating is water soluble
– The coating is quickly dissolved after swallowing
– The coating protects the enclosed drug from the environment
– The coating enhances the general appearance of tablets and permits imprinting of identifying manufacturer’s info.
– Disadvantages to sugarcoating tablets are,
– the time and expertise required in the coating process,
– the increase in size, weight, and shipping costs. * May be 50% larger and heavier than uncoated tablets - Film-coated tablets (F.C.T.):
These compressed tablets are coated with a thin layer of a polymer capable of forming a skin-like film over the tablet - Usually colored
- More durable, less bulky, and less time-consuming to apply than sugar-coatings.
- Designed to rupture and expose the core tablet at the desired location within the gastrointestinal tract
- Gelatin-coated tablets:
GElCAP,
– Capsule-shaped compressed tablets
– Facilitates swallowing and compared to unsealed capsules, gelatin tablets are more tamper-evident - Enteric-coated tablets (E.C.T.):
Have delayed release characteristics - Designed to pass unchanged through stomach intestines where the tablets disintegrate and allow drug dissolution.
- Mainly used when by-passing
the stomach to improve drug absorption - Buccal or sublingual tablets:
These are flat, oval tablets intended to be dissolved in the buccal pouch, or beneath the tongue through absorption through the oral mucosa
– An alternative for drugs that are poorly absorbed from the G.I. Tract
– Buccal tablets designed to erode slowly
– Sublingual tablets designed to provide rapid release
Buccal: In direction of the cheek Sublingual: Below or beneath the tongue
The dosage form must remain in place - Total area of absorption is low compared to
other routes- 100 to 170 cm2
– Taste must be bland, or not acceptable for use – must also be a non-irritant
– Drug should not discolor or erode teethLining of the epithelium is keratinized for buccal and
sublingual, but the epithelium for sublingual is thinner. - What does this tell us about drug absorption?
chewable:
Have a creamy base usually of specially flavored and colored mannitol
* Rapid disintegration when chewed or allowed to dissolve in mouth
* Ideally suited for children and adults who have difficulty swallowing solid dosage forms.
molded tablets
ablet triturates (TT) may be prepared by compression and by molding.
* In terms of appearance very soft and soluble
* Diluent: Lactose and Sucrose usually
* Designed for rapid dissolution
* Pharmacists may insert TT inside a capsule or
dissolved in liquids to provide accurate amounts
of potent drugs.
Instant Disintegrating/ Dissolving tablets * Extended Release Tablets (E.R.)
- Vaginal Tablets:
Also called vaginal inserts - Uncoated and bullet or ovoid shaped tablets * Inserted in vagina for localized effects
– Antibacterials for the treatment of Vaginitis caused by Hemophilus vaginalis or
– Antifungal for treatment of vulvo vaginitis candidiasis caused by Candida albicans and related species
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quality standards
dissolution
which tablet is designed for rapid dissolution
molded tablet (M: T)
* Designed for rapid dissolution
wet granulation
packaging and storage
dry granulation
lozenges
lollipops
Modified-Release Delivery Systems
Terminology- General types
Packaging and storage requirements
Candidates for extended release products
Factors affecting percutaneous absorption
- intracellular matrix is relatively polar in nature.
- Intercellular lipids are lipophilic.
- Permeation requires repeated partitioning between the polar environment and the lipophilic domain.
For the intercellular route
- Provide the only continuous route through the stratum corneum.
- The polar pathway is the diffusion of rate limiting region of very polar permeant.
- Less polar permeant through the lipid pathway
simple passive diffusion across SC: Vehicle, SC, epidermis, dermis
- size affects it as well:
Iontophoresis
- a method used to enhance permeability
- mechanisms: electrophoresis, electro-osmosis, increased permeability
how it works:
- put a patch on, this patch is a battery with a + and - end
- an electric current is passed from the positive side to the negative side of the patch battery
- the ionized drug comes from the positive side and follows the current but gets dropped off into the bloodstream.
- the counter ion (which is negative) moves to the negative side
Chemical enhancers
- one of the disadvantages of TDD because Contact allergic dermatitis (involves host immunological activity)
– Contact irritant dermatitis (direct toxic injury to cell membranes, cytoplasm, or nuclei) - helps with permeation
- Pharmacologically inert
- Non-toxic, non-irritating, non-allergenic
- Reliable and predictable
- Immediate recovery of the skin
(reversible disruption of the skin) - Compatible with the API
examples:
- Lipophilic solvents
Dimethylsulfoxide (DMSO)
Dimethylformamide (DMF)
2-Pyrrvolidinone
- Surface active agents
Sodium lauryl sulfate (SDS)
Dodecyl methyl sulfoxide - Two-component system
Propylene glycol-oleic acid
1,4 butane diol-linoleic acid - they strip lipids off of the stratum corneum therefore allowing drugs to go through
- ethanol
- glyceryl monoethyl ether
- monoglycerides
- isopropyl myristate
- lauryl alcohol (aka lauric acid, lauryl lactate)
- terpinol
- menthol
- D-limonene
- beta-cyclodextrin
- DMSO
- Polysorbates
- fatty acids
- bile salts
- N-methylpyrrolidone
- polyglycosylated glycerides
- 1-dodecylaza cyclohexane-2-one
- cyclopentadecalactone
- akyl-2-alkanoate ester
- 2-(n-nonyl)-1,3-dioxolane
Water As An Enhancer
- Hydration causes corneocyte swelling and keratin bundle dissociation
Mechanisms for Chemical Enhancers
- increase the partition of the drug into the stratum corneum.
- disrupt the highly ordered structure of the intercellular lipids.
- interact with intracellular proteins embedded in the corneocytes to increase the transcellular permeation.
Sonophoresis
- Ultrasonic refers to sound waves whose frequency is >20 KHz
- the movement of drugs through living skin and into soft tissue under the influence of an ultrasonic perturbation
- you have a power supply attached to an ultrasonic transducer attached to the skin and the applied formulation sends sound waves through the skin to allow chemicals to pass through the skin
Monolithic systems
is a type pf TDD
has a backing with a rate-controlling matrix containing drug then the adhesive
Examples of TDDSs on the market
Iontophoresis Products:
- E-Trans Fentanyl Patch (Alza, 2004).
- Indication: post-operation pain or cancer chronic pain.
- Patient self-controllable.
Estradiol
A natural hormone used for the relief of post- menopausal syndromes and osteoporosis.
st
* Oral dosed undergoes significant 1 pass
* Short half-life = 1 hr
* Not substantially metabolized by skin
* Convenient once to twice a week dosing on the trunk (abdomen, buttock)
Vivelle-Dot
Vivelle-Dot® contains estradiol in a multipolymeric adhesive. The system is designed to release estradiol continuously upon application to intact skin.
1. A translucent polyolefin film
2. An adhesive formulation containing estradiol, acrylic adhesive, silicone adhesive, oleyl alcohol, povidone, and dipropylene glycol
3. A polyester release liner.
Transdermal Scopolamine
Antimuscarinic drug, natural ingredient found in belladonna plant used for motion sickness
1st transdermal drug device approved by FDA
Non-irritating
Potent drug: 1 mg/72 hr
Short-half life (2.9 ± 1.2 h), anticholinergic side- effects when given orally
Scopolamine
MW = 303.35, pKa = 7.55-7.81.
* The Transderm Scop® film: 0.2 mm thick and 2.5 cm2 (1) Backing layer of tan-colored, aluminized, polyester film
(2) Drug reservoir: light mineral oil, and polyisobutylene
(3) Rate controlling microporous polypropylene membrane
(4) Adhesive formulation of mineral oil, polyisobutylene, and scopolamine.
(5) A protective peel strip of siliconized polyester, which covers the adhesive layer
Clonidine (Catapres-TTS)
An antihypertensive agent
Oral drug undergoes significant 1st pass
Highly lipid soluble
Low therapeutic concentration (0.2-2 ng/mL)
Once a week
4-layers: backing, reservoir, micro-porous membrane, adhesive formulation
Nitroglycerin
Antianginal drug used for prevention of angina pectoris due to coronary artery disease
A Vasodilator
Very short-half life (min)
Extensive 1st pass
Low dose (Cpss 1.2 – 10 ng/mL)
Tolerance is common for long term use
Side-effects include headache, dizziness, and hypotension, and skin irritation
Transderm-Nitro (Novartis) Nitro-Dur (Key)
Deponit (Schwarz Pharma)
Nicotine Patches
To provide nicotine replacement therapy to obtain plasma levels of nicotine that would prevent or lessen the severity of the withdrawal symptoms
Fentanyl (Duragesic®)
DURAGESIC® (fentanyl transdermal system) is a transdermal system providing continuous systemic delivery of fentanyl, a potent opioid analgesic, for 72 hours.
Fentanyl Patches (mylan)
1. Drug in adhesive Matrix Patch. 2. No rate controlling membrane.
Oxytrol (Oxybutynin) for Overactive Bladder
Layer 1 (Backing Film) is a thin flexible polyester/ethylene-vinyl acetate film that provides the matrix system with occlusivity and physical integrity and protects the adhesive/drug layer.
Layer 2 (Adhesive/Drug Layer) is a cast film of acrylic adhesive containing oxybutynin and triacetin.
Layer 3 (Release Liner) is two overlapped siliconized polyester strips that are peeled off and discarded by the patient prior to applying the matrix system.
OXYTROLTM Oxybutynin Transdermal System
OXYTROL is designed to deliver oxybutynin continuously and consistently over a 3- to 4-day interval after application to intact skin. OXYTROL is available as a 39 cm2 system containing 36 mg of oxybutynin. It has a nominal in vivo delivery rate of 3.9 mg oxybutynin per day through skin of average permeability
* Oxybutynin is an antispasmodic, anticholinergic agent.
Lidoderm (Endo Pharm)
Lidoderm (lidocaine patch 5%) is comprised of an adhesive material containing 5% lidocaine, which is applied to a non-woven polyester felt backing and covered with a polyethylene terephthalate (PET) film release liner. The release liner is removed prior to application to the skin. The size of the patch is 10 cm x 14 cm.
* Each adhesive patch contains 700 mg of lidocaine in an aqueous base.
* The Lidoderm® patch is the only topical analgesic indicated to treat the pain of postherpetic neuralgia (PHN).
* 12-hour once-daily dosing up to 3 patches at a time
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Lidoderm for Postherpetic Neurogalia (PHN)
PHN is the pain after the rash from shingles is gone
Shingles are caused by chicken- pox infection of nerves
Pain can last for 6 months
Zostrix cream
five-six times a day. It will take two to three weeks of use before the cream will start to work
Ortho-Evra (Ortho-McNeil Pharm)
- The ORTHO EVRA birth control patch is a highly effective, weekly hormonal birth control patch that is worn on the skin to prevent pregnancy. The patch is worn for one week and replaced on the same day of the week for three consecutive weeks, with the fourth week “patch-free.” ORTHO EVRA combines the efficacy of the birth control pill with once-a-week dosing.
- ORTHO EVRA contains two types of hormones: estrogen (ethinyl estradiol) and progestin (norelgestromin). Once you apply the Patch to your body, low doses of these hormones are continuously transferred through your skin and into your bloodstream to help prevent pregnancy.
- ORTHO EVRA can be worn in several discreet locations: buttock, abdomen, upper torso, or upper outer arm.
Membrane-controlled systems
has backing
drug reservoir
semipermeable membrean
adhesive
protective peel strip
What a patient should be advised
about TDDSs
Wash your hands with soap and water before applying patch. Dry hands completely.
* Clean the area chosen with soap and water. Rinse and wipe the area completely dry with a clean tissue.
* Apply the patch at the same times of day.
* Apply to a non-hairy area of the body.
* Do not apply the patch on skin folds or wear under tight clothing.
* Do not use the same spot all the time but rotate to different areas.
* Do not apply a patch directly after showering, bathing, or swimming.
* Open the package and remove and throw away the protective backing. Do not touch the sticky side.
* Do not cut the patches.
* Attach the patch to the skin and press firmly in place for 10-15 sec. Run your finger along the outside edge of the patch to seal it.
* Remove the throw away the patch after the specified time or before applying the next patch.
* Repeat the above procedure. 55
Ointments
Gels
Creams
pastes
plasters
glycerogelatins
Packaging semisolid preparations
Ophthalmic dosage preparations
advantages of TDD
Bypass hepatic “first pass”
* Bypass gastrointestinal incompatibility
* Reduce side effects
* Provide predictable and extended duration of activity
* Greater patient compliance
* Reversibility of drug delivery for removal
* Minimize inter- and intrapatient variation
Self administration
* Can use drugs with short half-life
* Administration of drugs with narrow therapeutic window
* Zero order release
* Controlled release for accurate dosing
* Control of plasma levels of potent drugs
disadvantages of TDD
- Permeation of drugs through human skin is limited
- Stratum corneum is the rate-limiting factor
- Only potent drugs that do not require high plasma levels are suitable for delivery
- Skin irritation from adhesives, API, excipients and enhancers
– Contact allergic dermatitis (involves host immunological activity)
– Contact irritant dermatitis (direct toxic injury to cell membranes, cytoplasm or nuclei) - Poor adhesive of transdermal devices
different types of TDD
parts of TDD
Polymeric matrix or matrices
- Drug (Pharmaceutically Active Ingredient)
- Permeation enhancers and other excipients
- Adhesives
