GelTech Labs

Automated swelling and degradation testing of Viatel™ PLGA-PEG-PLGA and PDLLA-PEG2000

Summary

GelTech held three Viatel™ samples from Ashland in PBS at 37 °C on Carousel for 14 days, weighing each automatically from 5 minutes on: an mPEG-PDLLA diblock and two lots of one PLGA-PEG-PLGA triblock grade. The two lots separated by 41% at Day 9, 9.94 against 7.07 g/g. Lot A peaked at 10.15 g/g on Day 12 and lost 18% by Day 14, while Lot B measured 7.2 g/g at Day 14. The lots ran one day apart, so a side-by-side run would confirm the gap. The diblock, tested neat, lost 91% of its peak mass within 8 hours.

What it means for Ashland

One 14-day run gave Ashland a quantitative swelling and degradation profile for each sample, and a way to compare lots of one grade on the same measure. The same instrument can extend the work to full degradation, drug release, pH and flow.

The Carousel chamber: a heated, sealed PTFE mesh cone in PBS with an inlet and outlet, and Lot A drawn in the mesh at Day 0, 4, 12 and 14

Two lots of one grade in the Carousel chamber

41%apart at Day 9, two lots of one grade

Lot A 9.94 g/g
Lot B 7.07 g/g

Swelling ratio at Day 9 in PBS at 37 °C, n = 3. The lots ran one day apart, so a side-by-side run would confirm the gap.

41%swelling gap between two lots of one grade at Day 9
14 daysof automated readings, from 5 minutes on
91%of peak mass the diblock lost within 8 hours, tested neat

Results

Swelling ratio is wet mass divided by initial mass. A ratio above 1 means the sample took up water, and a falling ratio means it's losing mass.

Lot A swells to 10.15 g/g at Day 12 and falls to 8.30 by Day 14; Lot B reaches 7.2 g/g; 41% apart at Day 9 — Mean ± SD band · n = 3 (n = 2 for PDLLA-PEG2000) · swelling ratio = wet mass ÷ initial mass · PBS, pH 7.4 · 37 °C · Lot B Days 10 to 13 interpolated between measured Days 9 and 14 (chamber drainage deviation)

The diblock peaks at 1.65 g/g at 5 minutes and falls to 0.15 g/g by 8 hours — Mean ± SD band · n = 3 (n = 2 for PDLLA-PEG2000) · swelling ratio = wet mass ÷ initial mass · PBS, pH 7.4 · 37 °C · Lot B Days 10 to 13 interpolated between measured Days 9 and 14 (chamber drainage deviation)

Materials and methods

Three Viatel samples ran in triplicate under one protocol: an amphiphilic diblock and two lots of a thermosensitive triblock. Every sample sat in a sealed PTFE mesh chamber in PBS at 37 °C, and Carousel drained and weighed each chamber on schedule, from 5 minutes through Day 14.

Diblock PDLLA-PEG2000 (mPEG-PDLLA)

An amphiphilic diblock that self-assembles into micelles in water, used to solubilize poorly soluble drugs. Tested neat in PBS, it peaked at 1.65 g/g at 5 minutes and fell to 0.15 g/g by 8 hours, so it's best tested formulated.

Lot A PLGA-PEG-PLGA triblock, thermosensitive

A triblock with a PEG core: liquid at room temperature, a gel at 37 °C, used for in situ forming injectable depots. Lot A swelled further, peaking at 10.15 g/g on Day 12, then lost 18% by Day 14 as it began to degrade.

Lot B PLGA-PEG-PLGA triblock, a second lot

The same triblock grade, from a second lot. Lot B swelled faster early, 3.2 g/g at 8 hours against Lot A's 2.4, then less far: 7.07 g/g at Day 9 and 7.2 g/g at Day 14.

Swelling and degradation · 14 daysStatic immersion, gravimetric

Setup. About 500 mg of sample sits in a sealed, conical PTFE mesh chamber in 100 mL of PBS, pH 7.4, static at 37 °C. Carousel drains and weighs the chamber at every timepoint.

Readout. Swelling ratio, wet mass ÷ initial mass, at 5, 10 and 30 min, 1, 2, 4 and 8 h, then daily to Day 14.

Static immersion, gravimetric. Flow-through and circulating modes use the same chamber.

First 8 hours · all threeStatic immersion, gravimetric

First 8 hours: Lot B reaches 3.2 g/g and Lot A 2.4 g/g, while PDLLA-PEG2000 peaks at 5 minutes and falls toward zero

Mean, n = 3 (n = 2 for PDLLA-PEG2000) · Lot B swells faster early, 3.2 against 2.4 g/g at 8 h

Static immersion, gravimetric. PBS, pH 7.4, 37 °C

Lot A · peak to Day 14Static immersion, gravimetric

Lot A from Day 9 to Day 14: near 10 g/g, a peak of 10.15 at Day 12, then 18% lower by Day 14

Mean ± SD, n = 3 · plateau near 10 g/g from Day 9, peak at Day 12, then 18% mass loss by Day 14

Static immersion, gravimetric. PBS, pH 7.4, 37 °C

Results summary

Measure	Diblock	Lot A	Lot B
Peak swelling (g/g)	1.65 at 5 min	10.15 at Day 12	7.2 at Day 14
Swelling at 8 h (g/g)	0.15	2.4	3.2
Swelling at Day 9 (g/g)	degraded	9.94	7.07
Change from peak	−91% by 8 h	−18% by Day 14	plateau

Methods. About 500 mg per chamber (0.47 to 0.58 g) in a conical PTFE mesh chamber with a 1 µm hydrophilic membrane, in 100 mL PBS, pH 7.4, lid closed, static at 37 °C. PLGA-PEG-PLGA was thawed from −20 °C before loading. Dry tare, then wet tare after a 3 min PBS pre-wet. Chambers were drained and weighed at 5, 10 and 30 min, 1, 2, 4 and 8 h, then daily to Day 14. Lot B Days 10 to 13 were excluded for a drainage deviation; the chart shows values interpolated between Days 9 and 14. The two lots ran one day apart, and a side-by-side run would confirm the gap. One PDLLA-PEG2000 chamber was excluded below tare. Mean values. Bench data. Viatel™ polymers supplied by Ashland.