In a healthy person insulin is produced and stored by the β-cells in the pancreas. In the absence of insulin or insulin deficiency, metabolism of carbohydrates, protein and fats are upset, ultimately resulting in Diabetes Mellitus. Clinically, diabetic patients require subcutaneous injection of exogenous insulin for the management of hyperglycemia. To maintain normal glucose levels in diabetic patients several new approaches are made like pancreatic islet cell transplant, insulin pumps, etc. Current practice for diabetes control relies on the sufferer measuring the level of glucose (sugar) in their blood then using their experience to judge how much insulin they should inject. They have to make predictions of how their future level of blood glucose will be affected by planned meals, exercise, etc. Failure to control blood sugar can result in a number of nasty side-effects such as blindness, kidney failure, heart disease and circulation problems. For reasons that are almost certainly related to current lifestyles, the number of diabetics in the population has increased significantly over the past few years. It has been estimated by the World Health Organisatation that: “ Diabetes cases in adults will more than double globally from 143 million in 1997 to 300 million by 2025 largely because of dietary and other lifestyle factors. “
Insulin pump is a mechanical device which allows patients to achieve and maintain blood glucose at near normal level on a constant basis. Continuous infusion of insulin through the use of these small and light-weight pumps eliminates the need for the patient to adhere rigidly to a regimen of multiple daily injections of insulin. This provides convenience, better adherence, and control over the disease process. Personal insulin pumps are currently beyond the ‘state of the art’ although I believe that larger-scale devices of this type have been developed for use in hospitals. The key difficulty (I suspect) in developing such a system is that blood sugar sensors are invasive and there are probably problems with infections in developing such a system. In future, it may be possible to measure blood sugar level by looking at secretions on the skin and this would then make automated pumps possible. Personal insulin pumps are available but these are not ‘smart’ systems and they rely on users to make decisions about how much insulin to inject and when to inject it. To read more about them, see: http://www.minimed.com/files/how.htm
Insulin pumps are designed to transmit drugs and fluids into the bloodstream without the repeated insertion of needles. These systems are particularly well suited to the drug delivery requirements of insulin, steroids, chemotherapeutics, antibiotics, analgesics, total parenteral nutrition, and heparin.
Early insulin infusion pumps were large bedside units used mainly in hospitals. Today, an insulin pump is the size and weight of a personal pager. It is a plastic-encased computer device that can be worn in a pocket or on the belt. A computer chip in the pump allows the patient to program the amount of insulin for the pump to release. An alarm can be set to warn the patient of a low battery or to indicate that the insulin was not delivered. For optimal working efficiency, the patient should change the infusion site every 2 or 3 days or whenever the blood glucose is above 240 mg/dL for two tests in a row. This may indicate that the infusion set is not working properly.
Implantable drug delivery systems are placed completely under the skin — usually in a convenient but inconspicuous location. The location for the pump can be the anterior subcutaneous tissue of the chest or abdomen, depending on the route of administration, since these sites are well protected and the implant is well concealed under the clothing.
Insulin delivery as a model implant pump system Conventional controlled-release formulations are designed to deliver drugs at a predetermined, preferably constant, rate. But insulin pumps are designed to necessitate either external control of the drug delivery rate or a volume of drug that is beyond the capabilities of existing controlled-release formulations. A pump can be distinguished from other controlled-release dosage forms in that the primary driving force for delivery by a pump is not the concentration difference of the drug between the formulation and the surrounding tissue, but, rather, a pressure difference. This pressure difference can be generated by pressurizing a drug reservoir, by osmotic action, or by direct mechanical actuation.
Characteristics for an ideal pump: The pump must deliver a drug within a range of prescribed rates for extended periods of time. It should be reliable. It should be chemically, physically and biologically stable. It should be compatible with drugs. The pump must be non-inflammatory, non-antigenic, non-carcinogenic, non-thrombogenic, and have overdose protection.
The pump must be convenient to use by the patient. It should have long reservoir and battery life and easy programmability. It should be implantable under local anesthesia. It should be able to monitor the status and performance of the pump. The interior and exterior of the pump must be sterilizable. Implantable pumps are expected to reliably deliver a drug at a prescribed rate for extended periods of time. The delivery-rate range of the pump must be sufficiently wide to provide both basal and enhanced delivery of the drug as dictated by the clinical situation. Alternately, there must be a capability for providing bolus injection of a drug in addition to basal delivery. A wide range of delivery rates is also needed to meet the expected patient-to-patient variability in demand for a drug and the individual patient’s changes in drug need during the course of therapy. Accuracy and precision of delivery must be maintained over extended periods of time. To justify the surgery associated with the implantation of a pump, this period must be at least 2 years or, preferably, 5 years. Sufficient biological, physical, and chemical stability of the drug within the pump are also required. In some situations, delivery of less than the required amount of a drug on the prescribed schedule can be considered dangerous; this can be corrected by reverting to conventional therapy. Overdoses, however, are not as easily correctable. An insulin overdose, for example, could result in severe hypoglycemia, coma, and death if not corrected with a rapid administration of glucose. An overdose can occur in a number of ways when drug delivery is by an implantable pump. For example, the life of a peristaltic pump is typically limited by the life of the tubing, which is repeatedly compressed. Splitting of the tube can result in contamination of non-hermatically sealed electrical components, electrical failure of the pump, and a drug overdose if there is a leak in the pump housing. Thus, mechanical failure is an important consideration because it not only affects the performance of the pump, but also is a safety concern. The presence of a finite reservoir life, a finite battery life, patient-to-patient variability in drug demand, or long-term changes in an individual patient’s drug demand requires that the implantable device be convenient to use. The reservoir of an implantable pump should be as large as possible. In the event that reservoir life is less than 2 to 5 years, then a simple means to refill the reservoir is required. Battery life should also be more than the 2- to 5-year pump life. The pump must also be easily programmable. Simple methods are required for initial programming of the pump in order to meet the delivery needs of the individual patient and for choosing among various delivery profiles during the course of therapy. The location for the pump can be the anterior subcutaneous tissue of the chest or abdomen, depending on the route of administration, since these sites are well protected and the implant is well concealed under the clothing.
Peristaltic pumps: It is based on the principle of a portable pump. They are safer since no drug can be delivered in case of an electrical malfunction. A titanium chamber is used to house the pump, electronics, and battery in order to provide a hermatic seal. This is important in order to prevent contamination. The housing is further coated for enhanced biocompatibility. Internal components are made from corrosion-resistant materials.
The most sophisticated of the emerging implant delivery technologies is the non-invasively programmable D rug A dministration D evice (DAD). The device’s titanium housing contains a refillable reservoir, an electronic control unit, a battery, and a peristaltic pump that provides drug delivery. A catheter routed to the site of administration is secured to the device. The reservoir is refilled or evacuated by percutaneous insertion of a syringe through the device’s self-sealing septum. The inert properties of the titanium and drug delivery surfaces allow the use of a wide variety of drugs (Figure)
The DAD contains an audible alarm system that alerts the patient to low battery power and low reservoir volume. For most applications, the entire system is implanted using only local anesthesia and can be performed on an outpatient basis. Advantages: Wide variety of drugs can be used. It enables potent substances or agents with narrow therapeutic indices to be delivered precisely. The risk of infection is reduced since the entire system is fully implanted.
Fluorocarbon propellant-driven pumps: The basic constant-rate pump consists of a hollow titanium disk that is divided into two chambers by freely moveable pistons. The inner chamber contains the drug solution, while the outer chamber contains a fluorocarbon liquid that exerts a vapor pressure well above atmospheric pressure at 37 0 C. The inner drug chamber is refilled through percutaneous injection by means of a self-sealing silicone rubber and Teflon septum. The pressure of the injection causes expansion of the inner chamber and compression of the fluorocarbon. Once filled, the fluorocarbon vaporizes and compresses the inner chamber. The drug solution is then forced through fine-bore Teflon capillary tubing, which acts as a flow regulator, and subsequently through an intravascularly located delivery catheter. Bacterial filters are included in the refill and delivery lines. Flow rate can be modified by changing the length of the capillary tubing or by changing the viscosity of the drug solution (e.g., high-molecular-weight dextran).
Osmotic pumps: It consists of a flexible, impermeable diaphragm surrounded by a sealed layer containing an osmotic agent at a particular concentration, which, in turn, is contained within a semi-permeable membrane. A stainless steel tube or a catheter is inserted into the innermost chamber for delivery. When the filled pump is placed in an aqueous environment, water diffuses into the osmotic agent chamber at a rate determined by the permeability of the surrounding membrane and the concentration of the agent. The absorbed water generates a hydrostatic pressure that acts on the flexible lining to force the drug through the pump outlet (Figure 2). An osmotic-pressure actuated, constant-rate pump has also been described with a freely moveable piston rather than a rubber diaphragm. The piston is used to maintain a constant pressure in a low osmotic pressure solution reservoir, which is separated from the high osmotic pressure fluid by a semipermeable membrane. Movement of solvent across the membrane increases the pressure on that side of the membrane, forcing drug solution out of a chamber, which is separated from the high osmotic pressure solution by a second freely moving piston. The freely moving piston on the low osmotic pressure side moves to lower the volume of that reservoir as the solvent moves across the membrane, thus, pumping the drug into the body.
Controlled-release micropump: An implantable pump has been developed utilizing diffusion across a rate-controlling membrane for basal delivery, which can be augmented by rapidly oscillating piston acting on a compressible disk of foam. Without an external power source, the concentration difference between the drug reservoir and the delivery site is sufﬁcient to cause diffusion of the drug to the delivery site (basal delivery). Augmented delivery is achieved without valves by repeated compression of the foam disk by a coated piston. The piston is the core of a solenoid, and compression is affected when current is applied to the solenoid coil (Figure 3). Interruption of the current causes the membrane to relax, drawing more drug into the foam disk for the next compression cycle. The basal rate is determined by the magnitude of the concentration or pressure difference and by the permeability of the rate-controlling membrane and other diffusion resistances between the reservoir and the outlet. The augmented rate is a function of the elastic properties of the foam, the force applied by the solenoid piston, and the frequency of compression.The augmentation arises from a pressure difference superimposed during piston movement on the basal-concentration gradient or from a mixing effect associated with piston movement.
SEMINAR PRESENTATIONTOPIC: INSULIN PUMPSSubject incharge:Mr. Junise VazhayilAsst. ProfessorDept. of PharmaceuticsAl Shifa College of PharmacyPresented by:Muhammed Fahad1stMPharm Pharmaceutics(3rdBatch)Al Shifa College of Pharmacy1
INTRODUCTIONINTRODUCTION• People with diabetes cannot make their own insulin, ahormone that is normally secreted by the pancreas.Insulin is essential to metabolise sugar and hencegenerate energy• Currently most diabetics inject insulin 2 or more timesper day, with the dose injected based on readings oftheir blood sugar level2
INSULIN PUMP• A personal insulin pump is an external device thatmimics the function of the pancreas• It uses an embedded sensor to measure blood sugarlevel at periodic intervals and• then injects insulin to maintain the blood sugar at a‘normal’ level3
• Designed to transmit drugs and fluids into bloodstream without repeated insertion of needles• well suited to the drug delivery requirements of:– insulin,– steroids,– chemotherapeutics,– antibiotics,– analgesics,– and heparin.4
Present Day Insulin PumpsPresent Day Insulin Pumps6
Insulin delivery system• Data flow model of software-controlled insulinpumpInsulinrequirementcomputationBlood sugaranalysisBlood sugarsensorInsulindeliverycontrollerInsulinpumpBloodBloodparametersBlood sugarlevelInsulinPump controlcommands Insulinrequirement7
Insulin Delivery as a Model Implant PumpSystem• Implantable drug delivery systems are placedcompletely under the skin — usually in aconvenient location.• Generally placed in the anterior subcutaneoustissue of chest/abdomen for concealment.9
Insulin Delivery as a Model Implant Pump System• designed to necessitate external control of the drugdelivery rate or volume of drug (unlike conventionalcontrolled-release formulations)• primary driving force for delivery is the pressurepressuredifferencedifference.– generated by pressurizing a drug reservoir with apump• by osmotic action (osmotic pumps),• by direct mechanical actuation.10
Characteristics for an ideal pumpCharacteristics for an ideal pump• Deliver drug within prescribed ratesprescribed rates for extended periods(2-5 yrs).• Accuracy & precision.• ReliableReliable.• Chemically, physically & biologically stablestable.• CompatibleCompatible with drugs.• Non-antigenic & non-carcinogenic.• Must have overdose protectionoverdose protection.11
• ConvenientConvenient to use.• Implantable by local anesthesia.• Able to monitormonitor the performance of the pump.• Must be sterilizablesterilizable.• Have wide delivery ratewide delivery rate for basal & bolus deliveries tomeet patient variability.• Long reservoir & battery life and easyprogrammability.Characteristics for an ideal pump:Characteristics for an ideal pump:12
Peristaltic PumpsPeristaltic Pumps• Construction:– Pump, electronics & battery.– Titanium chamber provide hermatic seal.– Further coatedto improve biocompatibilty.14
Peristaltic Pumps• Figure 1: Cross-sectional view of the DAD showing key components15
Drug Administration Device (DAD)Advantages: Use of wide variety of drugs. Precise delivery of potent & narrow therapeuticsubstances. Less risk of infection since it is fully implanted. Performed using local anesthesia & onoutpatient basis. Presence of alarm system makes the pumpmore safe.16
Controlled-release micropump• Diffusion across a rate-controlling membrane for basaldelivery.• Augmented by rapidly oscillating piston acting on acompressible disk of foam—achieved without valves byrepeated compression of the foam disk by a coatedpiston.20