FORMULATIONS USEFUL FOR SPRAY DRYING VACCINES
The present invention is directed to formulations for spray-drying viral particles, methods for spray drying such compositions, and pharmaceutical compositions and vaccines comprising the present spray-dried powders. The present formulations advantageously provide for spray-drying viral particles at low temperatures, thereby producing spray-dried viral powders having viral infectivities comparable to those of powders prepared by lyophilization of comparable formulations. The methods and compositions described herein advantageously provide substantially higher throughput and production rates for the production of viral powders. Further, spray-dried viral powders incorporating enteric polymers can be produced at low temperatures.
1 . A formulation for spray-drying comprising viral particles, sucrose, and cyclodextrin.
2 . The formulation of claim 1 , wherein said viral particles are adenoviral particles.
3 . The formulation of claim 1 , wherein said viral particles comprises an adenoviral vector that is replication competent.
4 . The formulation of claim 1 , wherein the cyclodextrin is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin or a mixture thereof.
5 . The formulation of claim 1 , wherein the total amount of sucrose and cyclodextrin is from about 5 wt % to about 15 wt % of said formulation.
6 . The formulation of claim 1 further comprising an excipient.
7 . The formulation of claim 1 further comprising raffinose, mannitol, lactose, starch or a mixture thereof.
8 . The formulation of claim 1 further comprising a spray aid.
9 . The formulation of claim 1 further comprising maltodextrin, lactose, talc, triethyl citrate, gelatin or a mixture thereof.
10 . The formulation of claim 1 further comprising a spray aid in an amount from about 3 wt % to about 15 wt %.
11 . The formulation of claim 1 further comprising a surfactant.
12 . The formulation of claim 1 further comprising polysorbates, poloxamers or a mixture thereof.
13 . The formulation of claim 1 further comprising a surfactant in an amount from about 0.05 wt % to about 1 wt %.
14 . The formulation of claim 1 is an aqueous formulation.
15 . The formulation of claim 1 , wherein the total solids content of the formulation is less than about 30 wt %.
16 . The formulation of claim 1 , wherein the total solids content of the formulation is from about 5 wt % to about 25 wt %.
17 . A spray-dried powder comprising viral particles, sucrose and cyclodextrin.
18 . A formulation for spray drying comprising viral particles and a carbohydrate, wherein the total solids content of the formulation is less than about 30 wt %.
19 . The formulation of claim 18 , wherein the carbohydrate is sucrose, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, raffinose, mannitol, lactose, starch or a mixture thereof.
20 . The formulation of claim 18 further comprising a surfactant.
21 . A formulation for spray drying comprising viral particles, a carbohydrate and an enteric polymer.
22 . The formulation of claim 21 , further comprising a surfactant.
23 . The formulation of claim 21 , wherein the enteric polymer is Eudragit® L 30 D-55.
24 . A spray-dried powder comprising viral particles, a carbohydrate and an enteric polymer.
25 . A method for large scale spray drying comprising spraying drying the formulation of claim 1 , 18 or 21 at an outlet temperature of less than about 40° C.
26 . The method of claim 25 , wherein the outlet temperature is less than about 30° C.
27 . A spray-dried powder produced by the method of claim 25 .
28 . A spray-dried powder made from the formulation of claim 1 , 18 or 21 .
29 . The spray-dried powder of claim 27 , wherein the viral activity of the viral particles is at least about 70% of the viral activity prior to spray drying.
30 . A pharmaceutical composition for oral administration comprising the spray-dried power of claim 27 .
31 . A vaccine comprising the spray-dried powder of claim 27 .
32 . A replication competent vaccine for oral administration comprising the spray-dried powder of claim 27 .
33 . The spray-dried powder of claim 28 , wherein the viral activity of the viral particles is at least about 70% of the viral activity prior to spray drying.
34 . A pharmaceutical composition for oral administration comprising the spray-dried power of claim 28 .
35 . A vaccine comprising the spray-dried powder of claim 28 .
36 . A replication competent vaccine for oral administration comprising the spray-dried powder of claim 28 .