Gastro retention using polymer cocoons

Figures & data

Table I. Characteristics of polymers synthesized.

Code	Comonomer	Weight % nonionic monomer	Infinite shear Viscosity (s^-−1)	Hydrodynamic diameter (nm)
K0	None	100	–	62
T0	AA	80	79	61
U0	AA	75	105	68
X0	AA	70	83	60
Y0	AA	60	86	63
YHMW	AA	60	–	72
ZZ0	AA	30	–	63
ZX0	AA	10	88	63
GHMW	DMAEA-MQ	80	46	62
FHMW	DMAEA-MQ	60	57	60
CHMW	DMAEA-MQ	30	55	76
BHMW	DMAEA-MQ	20	52	69
BvHMW	DMAEA-MQ	20	65	76

AA: Acrylic Acid; DMAEA-MQ: Dimethylaminoethylacrlyate methyl chloride.

Table II. Summary of the evaluation of polymer chemistry on cocoon formation.

Anionic polymer charge (wt%)	Anionic polymer grain size (mm)	Cationic polymer charge (wt%)	Cationic polymer grain size (mm)	Cocoon diameter at 24 h (mm)	Observations
− 20	0.4–0.6	+ 70	0.4–0.6	1.8 × 4.8	Sinks
− 25	0.4–0.6	+ 70	0.4–0.6	1.6 × 4.8	Sinks, Stable
− 30	< 0.4	+ 70	< 0.4	1.8 × 4.3	Floats
− 30	0.4–0.6	+ 70	0.4–0.6	1.8 × 4.3	Floats
− 30	< 0.6	+ 70	< 0.6	1.6 × 4.7	Floats
− 40	0.4–0.6	+ 70	0.4–0.6	1.5 × 5.0	Floats
− 40	< 0.6	+ 70	< 0.6	1.7 × 4.3	Floats
− 40	0.4–0.6	+ 80	0.4–0.6	1.8 × 5.0	Floats, Stable
− 40	0.4–0.6	+ 90	0.4–0.6	1.8 × 4.9	Floats
− 50	< 0.6	+ 70	< 0.6	1.4 × 3.4	Fragile
− 50	< 0.6	+ 80	< 0.6	1.8 × 4.8	Floats
− 70	< 0.6	+ 70	< 0.6	1.6 × 4.5	Disintegrates

Figure 1. Photograph of CHMW-X0 capsules of various sizes in 0.1N HCl, at 37°C. The time is indicated by the clock (h:m:s). Upper left: Gelatin 1; Upper right: Gelatin 00; Lower left: HPMC 00; Lower middle: Gelatin 000; Lower right: Gelatin-0EL CS. (a) Outset of the experiment, (b): after 31m, (c) after 16h47m.

Figure 2. Swelling behavior of several capsules over time, (a) percentage volume increase and (b) weight gain.

Table III. Summary of the effect of payload on swollen cocoon properties.

Anionic polymer charge (wt%)	Anionic polymer grain size (mm)	Cationic polymer charge (wt%)	Cationic polymer grain size (mm)	Cocoon diameter at 24 h (mm)	Loading/Comments
− 30	0.4–0.6	+ 70	0.4–0.6	1.8 × 3.7	30%, Strong
− 40	0.4–0.6	+ 80	0.4–0.6	1.9 × 4.6	30%, Strong
− 40	< 0.6	+ 70	< 0.6	1.4 × 3.5	30%, Weak
− 40	< 0.6	+ 70	< 0.6	1.1 × 3.0	50%, Weak
− 50	< 0.6	+ 70	< 0.6	1.1 × 2.6	30%, Weak
None	−	+ 20	0.4–0.6	–	Disintegrates
None	–	+ 40	0.4–0.6	2.0 × 4.2	30% Strong

Figure 3. Mechanical resistance to compression as a function of capsule chemistry and size.

Figure 4. Mechanical resistance to compression as a function of the particle size of the polymers used to fill the capsules.

Figure 5. Photographs of a Size 1 HPMC capsule under compression showing partial rupture (a) and complete rupture (b).

Figure 6. Controlled release experiments of ambroxol hydrochloride controlled released pellets alone and in HPMC size 00 capsules.

Figure 7. X-Ray of a Size 1 Gelatin capsule.

Figure 8. Photograph of the autopsy contents of a dog's stomach containing three Size 0 gelatin capsules.