Non-degradable polymers are inert, biocompatible and offer a simple means of controlling drug release by? What are some examples of nondegradable polymers?
By diffusion or swelling
- Examples of nondegradable polymers are cellulose derivatives, silicones and acrylics
- Suitable for long-term applications such as orthopaedic and dental implants
What are diffusion-controlled systems (non-BDG)? What are the two types?
Diffusion-controlled systems can be divided into reservoir type (i.e. a drug core is surrounded by a polymer coating) or matrix type (i.e. drug particles are dispersed in a polymer matrix)
What are swelling-controlled systems produced from (non-BDG)?
Swelling-controlled systems are produced from water- soluble, cross-linked polymers
What are non-degradable polymers characterised by?
Characterised by tissue/blood compatibility, durability, robustness of structure and mechanical strength
What do biodegradable polymers degrade into?
biodegradable polymers degrade into non-toxic monomers and by-products, that can be efficiently cleared by the body
- No invasive surgery needed after therapy is complete
What are approved pharmaceutical implants based on biodegradable polymers?
Include hormones, antitumour drugs and antibiotics
- Complex sequences of drug-releasing steps involving diffusion and erosion (either surface or bulk)
Why do implants have predictable and reproducible drug release and degradation profile for extended periods of time
due to their geometric structure
What does formulation involve for performed and injectable implants? What needs to be done at the beginning and end of therapy?
Formulation involves extrusion, compression moulding, solvent casting or melt casting of implants into the desired shape
- Invasive surgery needed to implant and/or remove them at the beginning and end of therapy
- Injectable implants take shape after implantation
What are the commonly used polymers in injectable implants?
Poly lactide glycolic acid (PLGA) and polylactic acid (PLA) are commonly used polymers
What is a gliadel (carmustine implant) wafer?
Gliadel® Wafer is an implant for intracranial use, containing carmustine [1, 3-bis (2-chloroethyl)-1-nitrosourea, or BCNU] homogeneously distributed in polifeprosan 20, a biodegradable polyanhydride copolymer (consists of poly [bis (pcarboxyphenoxy)] propane and sebacic acid in a 20:80 molar ratio), providing controlled release of carmustine
- It is a sterile, off-white to pale yellow wafer approximately 1.45 cm in diameter and 1 mm thick. Each wafer contains 7.7 mg of carmustine and 192.3 mg of polifeprosan 20
What is an eligard injectable implant?
Injectable PLGA suspension formulation containing leuprolide acetate, for subcutaneous injection at 1 to 6-month intervals (based on dose injected: 7.5 – 45 mg LA), to suppress testosterone levels for inhibiting prostatic tumour growth
- Injected into SC Space
- Polymers respond to water by precipitating and trapping leuprolide acetate in a solid implant
- Biodegradable polymers degrade by hydrolysis –> slowly releasing leuprolide acetate
How do azlet osmotic pumps work?
- ALZET pumps operate because of an osmotic pressure difference within the pump and tissue environment in which the pump is implanted
- The high osmolality causes water to flux into the pump through a semipermeable membrane which forms the outer surface of the pump
- The expanded osmotic layer compresses the flexible reservoir, displacing the test solution from the pump at a controlled, predetermined rate
The compressed reservoir cannot be refilled, therefore the pumps are designed for single-use only
For an azlet pump;
A) What is the rate of delivery?
B) What drugs is it suitable for?
C) What is the volume delivery rate? How long do they last for?
A)
- The rate of delivery is controlled by the water permeability of the pump’s outer membrane (semi-permeable membrane)
- Thus, the delivery profile of the pump is independent of the drug properties/formulation dispensed
B)
- Suitable for drugs of various molecular configurations, including ionized drugs and macromolecules
C)
- The volume delivery rate of ALZET pumps is fixed at manufacture: available with delivery rates between 0.11 and 10 μL/hr
- delivery durations between 1 day and 6 weeks
What are some applications of azlet pump?
- Primary use is research.
- ALZET osmotic pumps can be implanted subcutaneously or intraperitoneally following the animal size guidelines.
- Can also be connected to a catheter to deliver the pump contents directly into the venous or arterial systems, the brain, or into any organ or tissue
For Implanon NXT (progestion only implant);
A) What does it consist of?
B) How is the contraceptive effect achieved?
C) How is it inserted?
D) When to replace?
A)
- IMPLANON consists of a soft, flexible, rod-shaped implant, containing 68 mg etonogestrel, pre-loaded in the needle of a sterile disposable applicator
B)
- Contraceptive effect is achieved by suppression of ovulation, increased viscosity of the cervical mucus, and alterations in the endometrium.
- Efficacy >99.9%
C)
- Inserted subdermally, just under the skin at the inner side of the non-dominant upper arm. Inserted under aseptic conditions
D)
- IMPLANON must be removed no later than by the end of the third year
- Can be replaced with a new implant
How is implanon formulated? What does it consist of? What is the release rate?
- IMPLANON is off-white, non-biodegradable and 4 cm in length with a diameter of 2 mm
- Implant consists of an ethylene vinyl acetate (EVA) copolymer core, containing 68 mg of the synthetic progestin etonogestrel, surrounded by an EVA copolymer skin
- Once inserted subdermally, the release rate is 60 to 70 μg/day in Week 5 to 6 and decreases to approximately 35 to 45 μg/day at the end of the first year, to approximately 30 to 40 μg/day at the end of the second year, and then to approximately 25 to 30 μg/day at the end of the third year.
For testopel testosterone pellets;
A) How are they given?
B) What do they contain?
C) What are they used for?
D) Doses?
A)
- Testopel testosterone pellets for subcutaneous implantation
B)
- Each pellet contains 75mg crystalline testosterone; stearic acid and polyvinyl pyrrolidone (PVP).
C)
- Replacement therapy in conditions associated with deficiency or absence of endogenous testosterone
D)
- Dosage: 2 x 75mg pellets equivalent to weekly 25mg testosterone dipropionate injection
- Dosage guideline for replacement therapy in androgen deficient males: 150-450mg pellets every 3-6 months
How are microchips used?
- The microchips consist of hundreds of pinhead-sized reservoirs, each capped with a metal membrane, that store tiny doses of therapeutics or chemicals. An electric current delivered by the device removes the membrane, releasing a single dose
- The device can be programmed wirelessly to release individual doses for up to 16 years to treat
- diabetes, cancer, multiple sclerosis, and osteoporosis
-
Sterilisation by membrane filtration23
-
Sterility Testing19
-
Colligative Properties 1+255
-
Formulation of eye drops27
-
Cold sterilisation26
-
Parametric Release24
-
CDR and TPN36
-
DDS: Pulmonary23
-
DDS: Implant18
-
DDS: Nasal24
-
DDS: Intraocular26
-
Protein and Insulin38
-
DDS: Transdermal37
-
Drug targeting and nanotechnology 129
-
Drug targeting and nanotechnology 2 + 336
-
Recombinant Pharmaceuticals 1 and 238
