Pancreatic Enzyme Pancreatic Enzyme Delivery (PED) DeviceDelivery (PED) Device

Group MembersGroup Members: : Todd DhavaleTodd Dhavale

Erica OsadzinskiErica Osadzinski

AdvisorAdvisor: : Dr. Dennis C. StokesDr. Dennis C. Stokes Associate Prof. Pediatrics Pulmonary Associate Prof. Pediatrics Pulmonary

MedicineMedicine

What is Cystic Fibrosis (CF)?What is Cystic Fibrosis (CF)?

40,000 cases in the United States alone40,000 cases in the United States alone– 2,000 children are born with CF every year2,000 children are born with CF every year

Inherited disease which causes exocrine (outward Inherited disease which causes exocrine (outward secreting) glands in the body to fail to function normally. secreting) glands in the body to fail to function normally.

Mucus-producing exocrine glands often produce thick, Mucus-producing exocrine glands often produce thick, sticky secretions which plug-up ducts and other sticky secretions which plug-up ducts and other passageways. passageways.

This occurs in the lungs and intestines and interferes with This occurs in the lungs and intestines and interferes with breathing and digestion. breathing and digestion.

CF is not curable at this timeCF is not curable at this time

Effects of Cystic Fibrosis on Effects of Cystic Fibrosis on DigestionDigestion

Occurs in 8 out of 10 of all CF patientsOccurs in 8 out of 10 of all CF patients

Pancreatic enzymes do not reach intestinal tractPancreatic enzymes do not reach intestinal tract

Malabsorption occursMalabsorption occurs

Patients do not gain weight --growth impairmentPatients do not gain weight --growth impairment

Therefore, above average caloric intake is needed Therefore, above average caloric intake is needed along with supplemental enzymesalong with supplemental enzymes

Our major concerns are these Our major concerns are these effects on infantseffects on infants with CF with CF

The Current SituationThe Current Situation

Currently infants receive no supplemental enzymes Currently infants receive no supplemental enzymes

Supplemental enzymes are packaged in “microspheres” Supplemental enzymes are packaged in “microspheres” which are enclosed in capsules which infants are which are enclosed in capsules which infants are unableunable to to swallowswallow

Microspheres are made to protect the enzymes in the acidic Microspheres are made to protect the enzymes in the acidic environment of the stomachenvironment of the stomach

Microspheres release and activate the enzymes in the Microspheres release and activate the enzymes in the alkaline small intestine so absorption can occuralkaline small intestine so absorption can occur

Thus, there is a need for a device that can administer the Thus, there is a need for a device that can administer the microspheres to infants simultaneously with the formulamicrospheres to infants simultaneously with the formula

Requested device Requested device parameters for infants and parameters for infants and

small children:small children:

Eight hour night time feedingEight hour night time feeding

Dr. Stokes prescribes:Dr. Stokes prescribes:– 3-5 capsules (containing pancreatic 3-5 capsules (containing pancreatic

enzyme microspheres) per night time enzyme microspheres) per night time feedingfeeding

Our Solution: Our Solution: The PED The PED DeviceDevice

Delivers enzymes Delivers enzymes to infants to infants receiving receiving overnight overnight supplemental supplemental feedings via a feedings via a gastrostomy tube gastrostomy tube (G-tube)(G-tube)

Components of the PED Components of the PED DeviceDevice

Uses Uses CreonCreon brand brand microspheres microspheres suspended in suspended in fluid delivery fluid delivery vehicle, vehicle, Ora-Ora-PlusPlus

Components of the PED Components of the PED DeviceDevice

The vehicle-microsphere The vehicle-microsphere mixture is continuously mixture is continuously pumped into the G-tube pumped into the G-tube

where it will be combined where it will be combined with the formula via a ‘Y’ with the formula via a ‘Y’ connector,connector,

then enter the stomachthen enter the stomach

Alternate Solutions???Alternate Solutions???

Pre-mixing microspheres in formula?Pre-mixing microspheres in formula?– intactintact– crushedcrushed

Dry, Without Suspending Vehicle?Dry, Without Suspending Vehicle?– airair– gravity deposit in formulagravity deposit in formula

Implementing and testing our Implementing and testing our solutionsolution::

1) Researched pancreatic enzymes function1) Researched pancreatic enzymes function

2) Assessed the current methods of 2) Assessed the current methods of obtaining the necessary pancreatic obtaining the necessary pancreatic enzymesenzymes

3) Met with pharmacist and pediatric nurse 3) Met with pharmacist and pediatric nurse for advice and recommendationsfor advice and recommendations– 20-25mL20-25mL limit volume forlimit volume for Ora-PlusOra-Plus

4) Which Microspheres worked 4) Which Microspheres worked best?best?

Tested microsphere stability Tested microsphere stability in the fluid delivery vehicle:in the fluid delivery vehicle:

– Pancrecarb MS-8Pancrecarb MS-8 had too had too large of Microsphereslarge of Microspheres

– Pancrecarb MS-4Pancrecarb MS-4 had the had the smallest Microspheressmallest Microspheres

– But the But the PancrecarbPancrecarb brand brand proved to be unstable in proved to be unstable in the the Ora-PlusOra-Plus… …

Thus these Thus these Microspheres broke Microspheres broke down before reaching down before reaching the stomachthe stomach

Creon Pancrecarb MS-4

Pancrecarb MS-8

5) Our Choice: 5) Our Choice: Creon Brand Creon Brand microspheresmicrospheres

Creon brand Creon brand Microspheres are Microspheres are slightly larger than the slightly larger than the smallest, Pancrecarb smallest, Pancrecarb MS-4MS-4

Creon proved to Creon proved to remain stable in the remain stable in the Ora-Plus for around 8 Ora-Plus for around 8 hours, (over-night)hours, (over-night)

Pancrecarb only Pancrecarb only remained stable for a remained stable for a mere 1 hour mere 1 hour

6) PED Pump 6) PED Pump RequirementsRequirements

Need Need 20-25mL20-25mL of fluid vehicle for of fluid vehicle for overnight feedingovernight feeding

For 3-5 For 3-5 Creon 5Creon 5 Capsules over 8 Capsules over 8 hour period:hour period:

2020 mL mL / 8 / 8 Hrs Hrs = = 2.5 2.5 mL/HrmL/Hr

55 capsules / capsules / 2020 mL = mL = 1 capsule / 4 mL1 capsule / 4 mL

7) Which Pump works better?7) Which Pump works better? Delivers the minimum fluid Delivers the minimum fluid

vehicle volume necessary for vehicle volume necessary for overnight enzyme delivery:overnight enzyme delivery:

– SyringeSyringe– PeristalticPeristaltic

Our Choice: Our Choice: – SYRINGE PUMPSYRINGE PUMP– WHY?WHY?

8) Other factors8) Other factors

Integrate pump fittings with Integrate pump fittings with connectors to gastrostomy tube connectors to gastrostomy tube (G-Tube)(G-Tube)

DesignSafe AnalysisDesignSafe Analysis

Future Work:Future Work:

Improve the current crude PED Improve the current crude PED modelmodel::

– Solvay Pharmaceutical Funding?Solvay Pharmaceutical Funding?– Self-contained deviceSelf-contained device– Out-Patient UseOut-Patient Use