Examples of controlled release

Implantable devices:

Advantages include: Convenience, compliance, control and commercial, disadvantages surgery is need to be inserted/removed, possibility of failure, potency, reactions with body and commercial (time and money).

they can be used for pain, contraception, diabetes, incontinence, systemic infection, ocular and dental purposes. Contraceptives include rods, vaginal rings and IUD coil. Mirena is a diffusion-contolled DDS for local delivery and it is easily reversible. The coil is removed by pulling the strings of the device. Norplant and Jadelle (newer device where drug and matrix combined) rods involve 6 rods being implanted in the arm.

Intraocular delivery is also possible. Drug can be even inserted under sclera in the back of the eye. It is unpleasant to insert an implant in the eye, but is better than injections. RESISERT (diffusion-controlled delivery) was the first CR device for eye delivery and is used to treat chronic noninfectious uveitis lasts for 30months before removed by taking off the sutures and decreases chances of reoccurance of uveitis. The matrix device has a drug core and a polyvinyl membrane. IVATION INTRAVETREAL IMPLANT (diffusion-controlled DSS) is used for AMD, DME and glaucoma. It looks like a screw, but is tiny compared to a coin. It consists up an erodible polymer and it can stay in the sub-conjuctiva of the eye for around 2 years. MEDIDUR is an device which is injected/dropped at the back of the eye and replaced after 36months, but is currently under phase III clinical trials, VITRASERT lasts for 5-8months and OCUSERT is a device used once weekly instead of 28drops squeezed in the eye.

There is also a Pressure-responsive Intraocular implantable delivery device which works by electronically-controlled pump. It is inserted in the conjuctiva and a reservoir contains the drug. When neccesary an injection of drug is being done to refill the reservoir. The advantage is that instead of injecting the eye, the device is being punched. The device then self-heals and release the drug by repsonding to mechanical force.

Drug-eluting stents (diffusion or chemically controlled release) which is an artificial 'tube' inserted into a natural passage/conduit in the body to prevent, or counteract, a disease-induced, localized flow constriction (stenosis of blood vessels). Restenosis (amount of cells reinfiltered after stent loss) limits effectiveniness though. Used to deliver cytotoxic drug such as Paciltaxel.

Examples of osmotic delivery devices include: DUROS, a catheter direct drug specifically to 1 point protected by body all time. The drug is pushed out of the orifices by a semi-permeable membrane.

Examples of degradable devices include: DURIN (chemically-controlled DDS, drug and rate-limiting polymer mixed into fibre, rod or tablet), GLIADEL wafers used in the treatment of malignant gliomas.

Mechanical pumps are also available. An example is the one to control insulin release. It monitors glucose, transmits reading to pump and secrete insulin. There is also an implantable pump controlled by the phycisian. It is implanted every 3 months and contains 6000units of insulin. However, if pump fails, it will cause trouble to patients.

There are also mechanical pumps for intrathecal delivery for severe chronic tumour pain management with morphine sulphate.

Lastly, in the future, Micro-scale delivery will be feasible. In a microfibrated osmotic engine, water flow increases and pushes balloon upwards to the hole to be released and delivered to patients. Osmotic agent pushes drug dwon. The size of the device is tiny with V capacity of microL, so drug needs to be potent!

Controlled release microchip: a metal mould with conical holds with sealing top with erodible. Underneath insoluble polymer sealing. Only way drug escape is through top. Each hole can be filled with different polymers to give a pulsatile effect. It works via erosion and PLGA tailors the rate of erosion, by changing the lactic acid, hydrophobicity and MR (methyl groups) is increased, making it harder to degrade as opposed to the hydrophilic glycolic acid.

Controlled delivery devices

Controlled dlievery systems are preparations designed in such a way that they release rate or location of active drug is controlled. They are needed to reduce fluctuations in [plasma] (imp. For reducing side effects of narrow therapeutic window drugs), reduce dosing frequency (imp. for patient compliance), control delivery site (colon) for optimum activity and timed release the drug (e.g. pulsatile action for hormones or angina).

There are four main mechanisms for controlling Drug Release.

The first one is Diffusion-control DDS. When diffusion takes place through a non-porous or micro-porous membrane and water-insoluble polymers coat the drug core [(s)/(l)], the device is called Reservoir and the drug goes in solution when in aqueous environment. Monolithic devices is the second type of diffusion-control DDS. Diffusion takes place through bulk water-insoluble polymer, when water penetrates, drug in solution diffuses. The drug is dissolved in polymer solution prior to device formation and dispersed throughout the device. This tends to be used for implantable devices.

The second type of CDDS is Chemically-controlled ones, where diffusion is similar to the matrix monolithic device. Drug is dissolved in (natural or synthetic and water-soluble or water degradable) polymer solution prior to device formation and is released as the polymer matrix breaks down. Predominantly for long-term implantation. There are two subtypes: monolithic devices, where either pure polymer erodes (surface erosion, decreasing ph, increases autocatalytic degradation of polymer backbone by acid addition or SAVIT delivery technology where coating is non-erodible and active erodible matrix erodes at both ends) or combination of erosion and diffusion takes place (bulk erosion, PLGA is commonly used and FDA approved). Multiple drug can be delivered at specific times and locations through the CHRONOP delivery technology and alternative pulsative release is also possible, when at fixed time drug will erode from inside. This is particularly useful for prolonged GIT absorption. The second subtype is Pendant systems where hydrolysis pendant group to break it free and be released from the backbone and diffusion of bulk polymer takes place. The rate of release depends on the hydrolysis of ester. Also in the HLB ratio. The more hydrophobic functional groups of polymer, the more slow release rate.

The third type is Water penetration- controlled DSS. The drug is being delivered through osmosis (Water transport through semipermeable membrane to form concentration solution inside, drug is pushed out through the hole) or swelling (water penetration into glossy polymer). Osmosis can be direct or indirect and more controlled, depending on the needs. An example of an osmotic device is OROS which provides CR for 24hrs, can be used for high doses of poorly and highly soluble drugs and improve bioavailability. It has been used to improve PK profile of oxybutin. Swelling controlled devices is affected by polymer structure (physichochemical properties, x-linking), hydrophobicity (polymer and drug contribute) and drug (concentration). The more concentrated, the greater gradient outside and inside. The more hydrophilic (pectin), water enters in rapidly and increases swelling, hydrophobic compounds (HPMC) decrease swelling rate. Mixture of hydroxypropyl and methyl controls swelling rate. There are also devices that can control rate by erosion, swelling and diffusion. Properties of gel can also be tailored by LBG (nice, straight polymer):Xanthan (helical polymer stabilises H-bonding) ratio. When gel formulation is wetted, water ingress allows drug to diffuse out gel. GEMINEX delivery technology combines two drugs together in a bilayer with a unique release profile. By altering polymer properties we can change where and how quickly drug is released. Distance betwee polymer chains is also important when high amylose starch is being used in formulations, such as CONTRAMID. It is safe, compressible, biogegredable, can be chemically x-linked, has a high drug capacity, fexible release profiles and can release multiple drugs. There are more complex systems to, such as GEOMATRIX. It has a hydrophilic HPMC core with drug in it, changing the properties alter parameters of device and tailored released depends on drug barrier. Both layers can expands or it can swell thinly. Water penetration controlled DSS working by swelling are capable of 0 order, quick slow, slow-quick, binary, positioned, acce;erated, delayed and pulsatile release. Burst can also take place in the swelling mechanism and the thicker the membrane, the slower the release. Alginate is an example of a polysaccharide working in this way.

The fourth and last type of DSS is responsive DSS. Drug release can be controlled by temperature (some polymers undergo a sol-gel transition upon a temp. change), ph (changes in ionisation or cleavage of functional groups due to altered ph can affect sol-gel behaviour, drugs can be loeaded in acidic branched polymers and by repleiing drug can go out), chemicals, enzymes (GIT lots of bac. espesh in colon have enzymes that can be used in delivery systems and an increased drug plasma concentration is being observed as the drug is released by degrading enzymes), ultrasound, magnetism, light, mechanical force (disrupts matrix by compression, sqeezing drug out and allowing it to be released) and IR radiation (insulin released from nanoparticles).

Reflecting on aseptic practical

I have concluded that maybe it is better and safer for patients and me to work as a community pharmacist. Aseptic practical today was really useful to understand what can go wrong in the preparation of these products and how to handle syringes, which is different learning all these information theoretically or watching a youtube video from being in a lab preparing a injection product. I think that in my practical several things went wrong and I have actually realised how precise and responsible technicians and clinical pharmacists should be when dealing with such preparations. Also, through the practical, I have realised that I am actually needlephobic. :S Lastly, I have reflected on the option of doing a pre-registration in hospital and I have concluded that however interesting hospital pharmacy may be, I would enjoy more dealing with all the community health care cases and the business, management and marketing side of pharmacy. I like business&management anyway. I am finally more orientated on my final goal and the future carrer outcome of my degree.

THE SEVEN PRINCIPLES

1. MAKE THE CARE OF PATIENTS YOUR FIRST CONCERN
2. EXERCISE YOUR PROFESSIONAL JUDGEMENT IN THE INTERESTS OF
PATIENTS AND THE PUBLIC
3. SHOW RESPECT FOR OTHERS
4. ENCOURAGE PATIENTS TO PARTICIPATE IN DECISIONS ABOUT THEIR CARE
5. DEVELOP YOUR PROFESSIONAL KNOWLEDGE AND COMPETENCE
6. BE HONEST AND TRUSTWORTHY
7. TAKE RESPONSIBILITY FOR YOUR WORKING PRACTICES

Emulsions

http://www.pharmpedia.com/Emulsions

10 Diet Commandments for Pain Patients

ttp://health.msn.com/health-topics/pain-management/fibromyalgia/slideshow.aspx?cp-documentid=100246652&imageindex=1

Affinity vs Avidity in Immunology

http://science.kukuchew.com/2008/05/08/affinity-and-avidity/

Xanthomas

I was reading through a msn article today on cholesterol. You can find here: http://health.msn.com/health-topics/cholesterol/articlepage.aspx?cp-documentid=100252282&page=1&gt1=31007 and I didn't know what xanthomas are, so I have decided to check the term out.

Xanthomas are fat deposits found under the skin and it looks pretty much like this:

More information and pictures can be found in medline plus link:

http://www.nlm.nih.gov/medlineplus/ency/article/001447.htm