ORAL SOLID DOSAGE FORMS COMPRISING CANNABINOIDS
The present disclosure relates to drug-containing particles comprising one or more cannabinoids and a porous solid carrier. In embodiments, the one or more cannabinoids are adsorbed onto and/or in a porous solid carrier. In embodiments, the drug-containing particles exhibit improved solubility and bioavailability, among other beneficial properties. Methods of preparation and pharmaceutical compositions are also described.
1 . A drug-containing particle comprising:
a. a drug substance comprising cannabidiol, wherein the cannabidiol is present at an amount ranging from about 15% to about 40% by weight based on the total weight of the drug-containing particle;
b. a porous solid carrier at an amount ranging from about 10% to about 60% by weight based on the total weight of the drug-containing particle;
c. a lipophilic material at an amount ranging from about 20% to about 35% by weight based on the total weight of the drug-containing particle; and
wherein the porous solid carrier comprises a mesoporous silica or an amorphous silica,
wherein the porous solid carrier has at least one of:
an average pore volume of about 0.5 mL/g to about 2.5 mL/g;
an average surface area of about 250 m 2 /g to about 600 mg2/g; or
an average pore diameter of about 2 nm to about 50 nm, and
wherein the lipophilic material comprises:
mono-, di- and triglyceride esters of C8-C18 fatty acids;
mono-, di-, and triglyceride esters of lauric and stearic acids and PEG-6 mono- and diesters of lauric and stearic acids; or
propylene glycol monocaprylate; or combinations thereof.
2 . The drug-containing particle of claim 1 , wherein the porous solid carrier has an average pore volume of about 0.5 mL/g to about 1.9 mL/g.
3 . The drug-containing particle of claim 1 , wherein the porous solid carrier has an average pore volume of about 2 mL/g to about 2.5 mL/g.
4 . The drug-containing particle of claim 1 , wherein the porous solid carrier has an average surface area of about 375 m 2 /g to about 600 m 2 /g.
5 . The drug-containing particle of claim 1 , wherein the porous solid carrier has an average surface area of about 300 m 2 /g to about 400 m 2 /g.
6 . The drug-containing particle of claim 1 , wherein the porous solid carrier has an average surface area of about 320 m 2 /g to about 375 m 2 /g.
7 . The drug-containing particle of claim 1 , wherein the porous solid carrier has an average pore diameter of about 2 nm to about 50 nm.
8 . The drug-containing particle of claim 1 , wherein the porous solid carrier has an average pore diameter of about 15 nm to about 30 nm.
9 . The drug-containing particle of claim 1 , wherein the porous solid carrier comprises has an average surface area of about 400 m 2 /g to about 600 m 2 /g and an average pore volume of about 0.5 mL/g to about 1 mL/g.
10 . The drug-containing particle of claim 1 , wherein the porous solid carrier comprises has an average surface area of about 375 m 2 /g to about 500 m 2 /g and an average pore volume of about 2 mL/g to about 2.5 mL/g.
11 . The drug-containing particle of claim 1 , wherein the porous solid carrier has a porosity of about 60% to about 99%.
12 . The drug-containing particle of claim 1 , wherein the porous solid carrier has a porosity of about 60% to about 75%.
13 . The drug-containing particle of claim 1 , wherein the porous solid carrier has a surface area of about 250 m 2 /g to about 375 m 2 /g, and a porosity of about 60% to about 75%.
14 . The drug-containing particle of claim 1 , wherein the drug substance further comprises no more than about 0.5% by weight of active of cannabidiorcol (CBD-C1), no more than about 0.5% by weight of active of cannabidivarin (CBDV), or no more than about 0.2% by weight of active of cannabidibutol (CBD-C4).
15 . The drug-containing particle of claim 1 , wherein the cannabidiol is present in an amount ranging from about 20% to about 35% by weight based on the total weight of the drug-containing particle.
16 . The drug-containing particle of claim 1 , wherein the cannabidiol is present in an amount ranging from about 25% to about 35% by weight based on the total weight of the drug-containing particle.
17 . The drug-containing particle of claim 1 , wherein the cannabidiol is present in non-crystalline form as measured by X-ray powder diffraction.
18 . The drug-containing particle of claim 1 , wherein the porous solid carrier comprises a mesoporous silica.
19 . The drug-containing particle of claim 1 , wherein the porous solid carrier is present in an amount ranging from about 30% to about 50% by weight based on the total weight of the drug-containing particle.
20 . The drug-containing particle of claim 1 , wherein the porous solid carrier is a microparticle.
21 . The drug-containing particle of claim 1 , wherein the porous solid carrier has an average particle size of about 50 μm to about 150 μm.
22 . The drug-containing particle of claim 1 , wherein the lipophilic material comprises mono-, di- and triglyceride esters of C8-C18 fatty acids.
23 . The drug-containing particle of claim 1 , wherein the lipophilic material comprises mono-, di-, and triglyceride esters of lauric and stearic acids and PEG-6 mono- and diesters of lauric and stearic acids.
24 . The drug-containing particle of claim 1 , wherein the lipophilic material comprises propylene glycol monocaprylate.
25 . The drug-containing particle of claim 24 , wherein the porous solid carrier comprises mesoporous silica and has an average surface area of about 320 m 2 /g to about 375 m 2 /g and an average pore volume of about 1 mL/g to about 1.9 mL/g, and wherein the cannabidiol is present in an amount ranging from about 25% to about 35% by weight based on the total weight of the drug-containing particle.
26 . The drug-containing particle of claim 1 , wherein the lipophilic material comprises mono-, di-, and triglyceride esters of lauric and stearic acids and PEG-6 mono- and diesters of lauric and stearic acids, or propylene glycol monocaprylate.
27 . The drug-containing particle of claim 1 , further comprising one or more antioxidant, wherein the one or more antioxidants comprises alpha-tocopherol, β-carotene, ascorbic acid, ascorbyl palmitate, lecithin, butylated hydroxyanisole, butylated hydroxytoluene, monothiolglycerol, propyl gallate, or a combination thereof.
28 . The drug containing particle of claim 1 , wherein at least 50% of the cannabidiol is released from the drug-containing particle in 1 hour, as measured under USP 711 with a Type II apparatus at pH 6.8.
29 . A pharmaceutical composition comprising a plurality of the drug containing particles of claim 1 .