ORAL DISSOLVABLE FILM WITH HIGH LOAD OF POLYMERIC BINDER
The present invention relates to an oral dissolvable film (ODF), methods of orally administering the same, and methods of manufacturing the same. The ODF includes a high load of binder. Such an ODF, containing a high load of binder, can achieve the requisite physical and performance characteristics and can be manufactured on a commercial scale, while demonstrating that the ODF is safe and effective to consumers for its intended use. This also includes formulating and configuring the ODF to deliver the API as desired, via, e.g., enteral, transmucosal, sublingual, and/or buccal, when the administration is oral.
1 . An oral dissolvable film comprising:
(a) a film matrix comprising binders (i) and (ii):
(i) Kollicoat® Protect, Kollicoat® IR, or a combination thereof;
(ii) at least one additional binder;
(b) solvent comprising water;
(c) an active pharmaceutical ingredient (API); and
(d) pharmaceutically acceptable excipient comprising at least one of a filler, preservative, sweetening agent, co-solvent, plasticizer, flavoring agent, taste masking agent, colorant, anti-caking agent, coating agent, emulsifier, solubilizing agent, lipid, humectant, thickening agent, lubricant, adsorbent, suspending agent, disintegrating agent, permeation enhancer, saliva stimulating agent, release modifier, adjuvant, fragrance, surfactant, pH adjusting agent, buffering agent, stabilizer, and antioxidant;
wherein,
the binders in (a)(i) and (a)(ii) are present in an aggregate amount of at least 30 wt. % of the oral dissolvable film; and
the one or more binders in (a)(i) are present in an aggregate amount of at least 25 wt. % of the oral dissolvable film.
2 . The oral dissolvable film of claim 1 , wherein the at least one additional binder in (ii) is selected from the group consisting of sodium carboxymethyl cellulose (Na-CMC), hydroxypropyl methyl cellulose E3, hydroxypropyl methyl cellulose K3, hydroxypropyl methyl cellulose E5, hydroxypropyl methyl cellulose E15, methyl cellulose A3, methyl cellulose A6, methyl cellulose A15, hydroxypropyl cellulose, pullalan, sodium alginate, ethyl cellulose, lactose, Kollidon® K90, Kollidon® VA64, Kollidon® 12 PF, Kollidon® 17 PF, Kollidon® 25 PF, Kollidon® 30 PF, Kollidon® SR, polyvinyl alcohol, Soluplus®, Eudragit® RL100, Eudragit® EP O, chitosan, carrageenan, carbomer, xanthan gum, starch, maltodextrin, gelatin, microcrystalline cellulose, hydroxyethylcellulose, and combinations thereof.
3 . The oral dissolvable film of claim 1 , having a drug load of API of at least 25 wt. %.
4 . The oral dissolvable film of claim 1 , having a drug load of API of up to 45 wt. %.
5 . The oral dissolvable film of claim 1 , having a drug load of API of 30-40 wt. %.
6 . The oral dissolvable film of claim 1 , wherein the one or more binders in (i) are present in an aggregate amount of at least 30 wt. % of the oral dissolvable film.
7 . The oral dissolvable film of claim 1 , having a weight ratio of binder to API of at least 0.8.
8 . The oral dissolvable film of claim 1 , having a weight ratio of binder to API of 0.8 to 1.4.
9 . The oral dissolvable film of claim 1 , wherein the aggregate amount of binder and API is present in at least 59 wt. % of the oral dissolvable film.
10 . The oral dissolvable film of claim 1 , wherein the aggregate amount of binder and API is present in 65±6 wt. % of the oral dissolvable film.
11 . The oral dissolvable film of claim 1 , having a thickness of 0.2-0.7 mm.
12 . The oral dissolvable film of claim 1 , which is in a unit dosage form and having a mass of 180-260 mg.
13 . The oral dissolvable film of claim 1 , having a density of 0.65-0.85 g/cm 3 .
14 . The oral dissolvable film of claim 1 , having a dissolution of at least 90 wt. % at 5 minutes, as measured using a USP apparatus of 1 basket, 0.01 N HCl media, volume of 900-ml at a temperature of 37±0.5° C. mixed at 100 RPM that is sampled at 5, 10, 15, 30, 45, and 60 min.
15 . The oral dissolvable film of claim 1 , having a dissolution of 100 wt. % at 10 minutes, as measured using a USP apparatus of 1 basket, 0.01 N HCl media, volume of 900-ml at a temperature of 37±0.5° C. mixed at 100 RPM that is sampled at 5, 10, 15, 30, 45, and 60 min.
16 . The oral dissolvable film of claim 1 , exhibiting a high stability such that at least 90 wt. % of API remains in the oral dissolvable film, under accelerated stability conditions of 40±2° C., relative humidity (RH) 75±5%, over a period of time of >6 months.
17 . The oral dissolvable film of claim 1 , exhibiting a high stability such that at least 90 wt. % of API remains in the oral dissolvable film, under stability conditions of 25±2° C., relative humidity (RH) 60±5%, over a period of time of >6 months.
18 . The oral dissolvable film of claim 1 ,
substantially devoid of a carminative substance, such that any carminative substance present therein is present in less than 0.1 wt. %;
substantially devoid of an antifoaming agent, such that any antifoaming agent present therein is present in less than 0.1 wt. %; and
substantially devoid of a substances that lowers the surface tension of gas bubbles, such that any substances that lowers the surface tension present in less than 0.1 wt. %.
19 . The oral dissolvable film of claim 1 , which has a loss on drying (LOD) of 10±5 wt. %.