Spray drying process for low aspect ratio particles comprising poly[(methyl methacrylate)-co-(methacrylic acid)]
Embodiments of a spray-drying process for producing low aspect ratio particles of poly[(methyl methacrylate)-co-(methacrylic acid)] (PMMAMA) are disclosed. In some examples, at least 95% of PMMAMA-containing particles made by the process have an aspect ratio <10. The particles may further include an active ingredient and/or an excipient.
1. A process for spray drying poly[(methyl methacrylate)-co-(methacrylic acid)] (PMMAMA) comprising:
(a) providing a spray solution comprising an active agent and at least 5 wt % PMMAMA dissolved in a solvent, the solvent selected from methanol, ethanol, mixtures of acetone and water, mixtures of dichloromethane and ethanol, mixtures of dichloromethane and methanol, mixtures of ethanol and water, mixtures of methanol and water, mixtures of methanol and acetone, mixtures of methanol, acetone and water, mixtures of methyl ethyl ketone and water, or mixtures of tetrahydrofuran and water;
(b) introducing the spray solution into an atomizer a feed rate of at least 3 kg/hr and atomizing the spray solution into a chamber to form droplets;
(c) introducing a drying gas into the chamber at a flow rate of at least 72 kg/hr to dry the droplets and form a powder comprising PMMAMA containing particles, wherein a ratio of the drying gas flow rate to the spray solution feed rate is at least 5; and
(d) collecting the powder from the chamber, wherein the temperature of the drying gas at an outlet of the chamber is <55° C.,
wherein at least 95% of the PMMAMA-containing particles have an aspect ratio <10.
2. The process of claim 1 wherein a temperature of the drying gas at an inlet of the chamber T inlet and a wt % of the PMMAMA in the spray solution C soln are selected to provide a dimensionless solvent parameter DSP <1.2
D
S
P
=
(
T
inlet
-
T
boil
T
boil
)
(
C
skin
-
C
soln
C
skin
)
0.75
(
Δ
H
vap
5
4
0
)
1.25
where T boil is the boiling temperature of the solvent, C soln is a wt % concentration of the polymer in the solvent at which skinning occurs, and ΔH vap is the standard enthalpy of vaporization in J/g of the solvent.
3. The process of claim 2 wherein the temperature of the drying gas at an inlet of the chamber T inlet and the wt % of the PMMAMA in the spray solution C soln are selected to provide a dimensionless solvent parameter DSP <1.
4. The process of claim 1 wherein the ratio of the drying gas flow rate to the spray solution feed rate is from 5 to 16.
5. The process of claim 1 wherein the solvent comprises methanol.
6. The process of claim 1 wherein the temperature of the drying gas, when introduced into the chamber, is <165° C.
7. The process of claim 1 wherein the spray solution comprises 5-9 wt % PMMAMA.
8. The process of claim 1 wherein the solvent comprises acetone.
9. The process of claim 8 wherein the temperature of the drying gas, when introduced into the chamber, is ≤100° C.
10. The process of claim 1 wherein the spray solution comprises 5-7 wt % PMMAMA.
11. The process of claim 1 wherein the PMMAMA has a free carboxyl group to ester group ratio of from 1:0.8 to 1:2.2.
12. The process of claim 1 wherein at least 95% of the PMMAMA-containing particles have an aspect ratio ≤5.
13. The process of claim 1 wherein a throughput of the process is >180 g of powder per hour.
14. The process of claim 1 wherein the spray solution further comprises an excipient.