Field of the invention:
The present invention provides a solid dispersion of l,3-thiazol-5-y!methyl [(2R,5R)-5-{[(2S)2-[(methyl{[2Kpropan-2-yl)-l,3-thiazol-4-yI]methyl}carbamoyI)amino]-4-(morpholin-4yl)butanoyl]amino}rl,6-diphenylhexan-2-yl]carbamate compound of formula-1 with one or more pharmaceutical acceptable carrier. The compound of formula-1 is represented by the following structural formula.
The present invention also provides a process for the preparation of the solid dispersion of the compound of formula-1.
Background of the invention:
Cobicistat known by chemical name of l,3-thiazoI-5-ylmethyl [(2R?5R)-5-{[(2S)2-[(methyllP-Cpropan^-yO-l^-thiazol^-yljmethylJcarbamoyOaminol^^morpholin^yl) butanoyl] amino}-l,6- diphenylhexan-2-yl]carbamate herein after referred as "formula-1". Cobicistat is a component of a four-drug, fixed-dose combination for HIV treatment Elvitegravir/Cobicistat/Emtricitabine/Tenofovir (known as the "Quad Pill" or Stribild®). The Quad Pill/Stribild was approved by the FDA in August 2012 for use in the United States. This is also approved in US under the brand name of TYBOST®.
Cobicistat is a potent inhibitor of cytochrome P450 3A enzymes, including the important CYP3A4 subtype. It also inhibits intestinal transport proteins, increasing the overall absorption of several HIV medications, including atazanavir, darunavir, and tenofovir alafenamide fumarate.

US Patent No. 8148374 discloses cobicistat, its pharmaceutical^ acceptable salts and it's pharmaceutical composition.
Cobicistat (Tybost, and component of Stribild, Gilead) is a novel cytochrome P450 (CYP) enzyme (CYP3A4) inhibitor used as a "booster" in combination with some HIV treatments, e.g. protease inhibitors, to reduce their metabolism during absorption and so increase the amount of unchanged drug reaching the systemic circulation. Ritonavir is also used as such a boosting agent but cobicistat differs in that it has no anti-viral activity of its own and is purely used to modify pharmacokinetics.
Cobicistat drug substance does not occur in crystalline form and is isolated as amorphous, hygroscopic solid foam of low glass transition temperature which readily transforms under ambtent conditions via a moisture and temperature-driven phase transformation into a rubber-like material that is difficult to process into dosage forms. The removal of the absorbed moisture and reversion to the original solid form does not occur.
International patent publication number WO 2009/135179 Al discusses the difficulties associated with processing the compound of formula-1 and describes combining the compound of formula-1 with solid carrier particles such as silicon-dioxide to improve the physical properties of the resulting solid material. But the silicon-dioxide carrier particles contribute to the overall weight and volume of the solid so that significantly more material is required in a formulation to achieve a given dose of the compound of formula-1. Accordingly, there is a need for solid forms of the compound of formula-1 that have the beneficial properties of the solids described in WO2009/135179 Al but lack the inert carrier particles that contribute to the weight and the volume of the solid.
By adsorbing onto silica by evaporation from dichloromethane solution of drug as part of the isolation of the cobicistat, a free flowing powder is produced.
The finished dosage form using the adsorbate showed bio-equivalence for cobicistat with dosage forms prepared by the ethanol/water high shear granulation process. For

cobicistat, formulation technology has dealt with challenging physical properties of an active pharmaceutical ingredient and provided an approach to improved handling and manufacturing of dosage forms.
Several methods to improve the dissolution characteristics of compounds have been reported, including particle size reduction, formation of solvates, complexes and micro spheres. Additionally, attempts have been made to improve bio-availability provided by solid dosage forms by forming solid dispersions of drugs. Solid dispersions create a mixture of a poorly water soluble drug and highly soluble carriers. Solid dispersions may increase bio¬availability by decreasing the energy required for solubilizing the drug and increasing the stability of the drug in solution. Traditionally these methods carry inherent limitations concerning physical stabilities of the solid dispersion on storage, problems with grinding or difficulty of removal of the solvent. Furthermore, it is important that the drug released from the solid phase does not precipitate in the small intestine tract but remains water-soluble in the aqueous fluids of the small intestine tract, since such precipitation results in low bio¬availability.
The present invention provides solid dispersions having more stability and greater bioequivalence.
Brief description of the invention:
The first aspect of the present invention is to provide a solid dispersion of 1,3-thiazoI-5-ylmethyl[(2R,5R)-5-{[(2S)2-^
carbamoyl)amino]-4-(morpholin-4yl)butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate compound of formula-1 with one or more pharmaceutically acceptable carrier.
The second aspect of the present invention is to provide a solid dispersion of the compound of formula-1 in combination with cellulose derivatives.
The third aspect of the present invention is to provide a process for the preparation of a solid dispersion of l,3-thiazol-5-ylmethyl[(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-
4

l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(mo
hexan-2-yl]carbamate compound of formula-1 in combination with one or more
pharmaceutical^ acceptable carrier.
Brief description of the Figures:
Figure 1: Illustrates the PXRD pattern of solid dispersion of the compound of formula-1
with MCC in the ratio of 1:1.
Figure 2: Illustrates the PXRD pattern of solid dispersion of the compound of formula-1
with MCC in the ratio of 1:2.3.
Figure 3: Illustrates the PXRD pattern of solid dispersion of the compound of formula-1
with HPMC in the ratio of 1:1.
Detailed description of the invention:
The present invention provides a solid dispersion of l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-ls3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate and process for its preparation thereof.
A conventional method for the manufacture of a solid dispersion relates to a fusion process which is characterized by melting a drug substance and a pharmaceutical acceptable carrier together at elevated temperature and, then, cooling the melt to solidify. Another conventional method for the manufacture of a solid dispersion relates to a solvent process which is characterized by dissolving a drug substance and a pharmaceutical acceptable carrier in an appropriate solvent and, then, removing the solvent. Additional method for the manufacture of a solid dispersion relates to mixing a drug substance and a pharmaceutical acceptable carrier through milling.
As used herein the term a "solid dispersion" is a drug-containing pharmaceutical bulk substance in which the drug is dispersed in a pharmaceutical acceptable carrier such as a polymer, cellulose derivative, a co-polymer, or a mixture thereof.
5

As used herein the term "suitable solvent" used in the present invention refers to "hydrocarbon solvents" such as n-hexane, n-heptane, cyclohexane, pet ether, toluene, pentane, cycloheptane, methylcyclohexane, m-, o-, or p-xylene and the like; "ether solvents" such as dimethoxymethane, tetrahydrofuran, 1,3-dioxane, 1^4-dioxane, furan, diethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, anisole, t-butyl methyl ether, 1,2-dimethoxy ethane and the like; "ester solvents" such as methyl acetate, ethyl acetate, isopropyl acetate, n-butyl acetate and the like; "polar-aprotic solvents such as dimethylacetamide (DMA), dimethylformamide (DMF), dimethylsulfoxide (DMSO), N-methylpyrrolidone (NMP) and the like; "chloro solvents" such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride and the like; "ketone solvents" such as acetone, methyl ethyl ketone, methyl isobutylketone and the like; "nitrile solvents" such as acetonitrile, propionitrile, isobutyronitrile and the like; "alcoholic solvents" such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, 2-nitroethanol, 2-fluoroethanoI, 2,2,2-trifluoroethanol, ethylene glycol, 2-methoxyethanol, I, 2-ethoxyethanol, diethylene glycol, 1, 2, or 3-pentanol, neo-pentyl alcohol, t-pentyl alcohol, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol, phenol, or glycerol and the like; "polar solvents" such as water or mixtures thereof.
As used herein the term "pharmaceutical^ acceptable carrier" as used herein, refers to both polymeric and non-polymeric carriers; hydrophilic and hydrophobic carriers; cellulose derivatives; polyvinylpyrrolidone (PVP) and copovidone.
As used herein the term suitable cellulose derivatives used in the present invention refers to cellulose acetate, cellulose nitrate, cellulose xanthate, carboxy methyl cellulose, micro crystalline cellulose herein referred as "MCC", methyl cellulose, ethyl cellulose, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC) and hydroxy ethyl cellulose and ploymers such as suitable water soluble polymer is a chemically modified cellulose and/or cellulose ether, and in particular is selected from the group consisting of alkylcellulose, e.g. methylcellulose, ethylcellulose, propylcellulose; hydroxalkylcellulose,

e.g. hydroxy methylcellulose, hydroxyethyl cellulose, hydroxypropylcellulose; hydroxyalkyl alkylcellulose, e.g. hydroxyethyl methylcellulose (HEMC), hydroxypropylmethylcellulose (HPMC); carboxyalkylcellulose, e.g carboxymethylcellulose (CMC), carboxymethyl hydroxyethylcellulose (CMHEC), hydroxyethylcarboxy methylcellulose (HECMC), sodium carboxymethylcellulose, cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose acetate (HPMCA), hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMC-AS) or mixtures thereof.
The first aspect of the present invention provides a solid dispersion of l,3-thiazol-5-ylmethyl[(2R,5R)-5-{[(2S)2-[(m^
amino]-4-(morpholin-4yl)butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate compound of formula-1 in combination with one or more pharmaceutical^ acceptable carrier.
In the present invention, the composition of the solid dispersion consist of a ratio of the amount of the compound of formula-1 to the amount of the pharmaceutical^ acceptable carrier therein ranges from about 1:0.1 to 1:10 by weight. The composition of Cobicistat with pharmaceutical^ acceptable carrier, preferably MCC, PVP, HPMC, HPC or HPMC-AS is about 1:0.1 to 1:10.
The second aspect of the present invention provides a solid dispersion of the compound of formula-1 in combination with cellulose derivatives.
Preferred embodiment of the present invention provides a solid dispersion of the compound of formula-1 in combination with microcrystalline cellulose.
Another preferred embodiment of the present invention provides a solid dispersion of the compound of formula-1 in combination with HPMC.
The third aspect of the present invention provides a process for the preparation of a
solid dispersion of l,3-thiazol-5-ylmethyl[(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l,3-
thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl]amino}-l,6-diphenyl
hexan-2-yl]carbamate compound of formula-1, comprising of the following steps:
7

a) Adding a suitable solvent to l,3-thiazol-5-ylmethyl[(2R,5R)-5-{[(2S)2-[(methyl{[2-(prppan-2-yl)-l,3-thiazol-4-yI]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl]amino}-l,6-diphenyl hexan-2-yl] carbamate,
b) adding a pharmaceutically acceptable carrier to the reaction mixture,
c) stirring the reaction mixture,
d) isolating the solid dispersion of l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l53-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl] amino}-l,6-diphenylhexan-2-yl] carbamate compound of formula-1.
Wherein,
in step-a) the suitable solvent is selected from alcohol solvents, chloro solvents, ester
solvents, polar aprotic solvents, ketone solvents,.hydrocarbon solvents and polar solvent
like water or mixture thereof;
in step-b) the suitable pharmaceutical^ acceptable carrier selected from cellulose
derivatives such as cellulose acetate, cellulose nitrate, cellulose xanthate, carboxy methyl
cellulose, micro crystalline cellulose, methyl cellulose, ethyl cellulose and hydroxy ethyl
cellulose; polyvinylpyrrolidone.
in step-d) isolation may be affected by removing the solvent. Suitable techniques which
may be used for the removal of solvent include filtration, using a rotational distillation
device such as a Buchi Rotavapor, spray drying, agitated thin film drying ("ATFD"),
freeze drying (lyophilization), and the like or any other suitable technique.
The preferred embodiment of the present invention provides a process for the preparation of a solid dispersion of l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl] amino}-!,6-diphenyl hexan-2-yl] carbamate compound of formula-1 in combination with MCC, comprising of the following steps:
a) Adding dichloromethane to l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl] amino}-l,6-diphenyl hexane-2-yl] carbamate,
b) adding micro crystalline cellulose to the reaction mixture,

c) stirring the reaction mixture,
d) distilling off the solvent completely from the reaction mixture to provide a solid dispersion of l,3-thiazol-5-ylmethyl [(2R35R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l,3-thiazol-4-yl]methyI}carbamoyl)amino]-4-(morphoIin-4yl)butanoyl]amino}-l,6-diphenyl hexan-2-yl] carbamate compound of formula-1 with MCC.
Another preferred embodiment of the present invention provides a process for the preparation of an solid dispersion of l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl]amino} -l,6-diphenylhexan-2-yl]carbamate compound of formula-1 in combination with HPMC, comprising of the following steps:
a) Adding dichloromethane to l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl] amino}-l,6-diphenyl hexan-2-yl] carbamate,
b) adding hydroxypropyl methylcellulose to the reaction mixture,
c) stirring the reaction mixture,
d) distilling off the solvent completely from the reaction mixture to provide solid dispersion of l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l,3-thiazol-4-yl] methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl]amino}-l,6-diphenylhexan-2-yl] carbamate compound of formula-1 in combination with HPMC.
Preferred solid dispersions are "solid solutions", where the dispersion of the components is such that the system is chemically and physically uniform or homogeneous throughout or even consists of one phase as defined by measurement of thermodynamic properties of the system, e.g. cobicistat and a pharmaceutical^ acceptable carrier form a system that is chemically and physically uniform or homogeneous throughout or even consists of one phase as defined by measurement of thermodynamic properties of the system.
The invention also encompasses pharmaceutical compositions comprising a solid dispersion of l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)butanoyl]amino}-l,6-diphenyl

hexan-2-yl]carbamate and one more pharmaceutical excipients. As used herein, the term "pharmaceutical compositions" or "pharmaceutical formulations" include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, or injection preparations.
Pharmaceutical compositions containing a solid dispersion of l,3-thiazol-5-ylmethyl[(2R,5R)-5-{[(2S)2^(me%^
amino]-4-(morpholin-4yl)butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate of the invention may be prepared by using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, surface active agents, and lubricants. Various modes of administration of the pharmaceutical compositions of the invention can be selected depending on the therapeutic purpose, for example tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, or injection preparations.
P-XRD Method of Analysis:
PXRD analysis of compounds produced by the present invention were carried out using BRUKER/AXS X-Ray dififractometer using Cu Ka radiation of wavelength 1.5406 A0 and continuous scan speed of 0.03°/min.
The process described in the present invention was demonstrated in examples illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention.
Examples: Example-1:
Preparation of solid dispersion of l,3-thiazol-5-yImethyl [(2R,5R)-5-{[(2S)2-[(methyl {[2-(propan-2-yl)-l,3-thiazol-4-yI]methyl}carbamoyl)amino]-4-(morpholin-4yI) butanoyl]a mino}-l,6-diphenylhexan-2-yl]carbamate (Formula-1) in combination with MCC (in the ratio of 1:1)

Dichloromethane (10 ml) was added to l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl {[2-(propan-2-yl)-lJ3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl) butanoyl] amino}-l,6-diphenylhexan-2-yl]carbamate (0.5 gms) at 25-30°C. Micro crystalline cellulose (0.5 gms) was added to the reaction mixture at 25-30°C and stirred for 30 minutes 5 at the same temperature. Distilled off the solvent completely from the reaction mixture to get the title compound.
Yield: 0.65 gms.
The PXRD pattern of the obtained compound was depicted in figure-1.
0 Example-2:
Preparation of solid dispersion of l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl {[2-(propan-2-yl)-l,3-thiazol-4-yl]methyI}carbamoyl)amino]-4-(morpholin-4yl) butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate (Formula-1) in combination with MCC (in the ratio of 1:1.5)
5 Dichloromethane (10 ml) was added to l,3-thiazoI-5-ylmethyl [(2Rs5R)-5-{[(2S)2-
[(methyl {[2-(propan-2-yl)-l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl) butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate (0.5 gms) at 25-30°C. Micro crystalline cellulose (0.75 gms) was added to the reaction mixture at 25-30°C and stirred for 30 minutes at the same temperature. Distilled off the solvent completely from the reaction mixture to get
0 the title compound. Yield: 1.9 gms.
Example-3:
Preparation of solid dispersion of l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl 5 {[2-(propan-2-yl)-l,3-thiazol-4-yl]methyl}carbamoyI)amino]-4-(morpholin-4yl)
butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate (Formula-1) in combination with MCC (in the ratio of 1:2.3)
Dichloromethane (10 ml) was added to l,3-thiazol-5-ylmethyl [(2R55R)-5-{[(2S)2-
[(methyl{[2-(propan-2-yl)-l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yl)
0 butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate (0.3 gms) at 25-30°C. Micro crystalline
11

cellulose (0.7 gms) was added to the reaction mixture at 25-30°C and stirred for 30 minutes at the same temperature. Distilled off the solvent completely from the reaction mixture to get the title compound.
Yield: 0.6 gms.
5 The PXRD pattern of the obtained compound was depicted in figure-2. Example-4:
Preparation of solid dispersion of l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl {[2-(propan-2-yI)-l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morphoIin-4yl) butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate (Formula-1) in combination with
0 HPMC (in the ratio of 1:1)
Dichloromethane (10 ml) was added to l,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)2-[(methyl{[2-(propan-2-yl)-l,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4yI) butanoyl]amino}-l,6-diphenylhexan-2-yl]carbamate (0.5 gms) at 25-30°C and stirred for 20 minutes at the same temperature. Hydroxypropyl methyl cellulose (0.5 gms) was added to the
5 reaction mixture at 25-30°C and stirred for 30 minutes at the same temperature. Distilled off the solvent completely from the reaction mixture to get the title compound. Yield: 0.6 gms.
The PXRD pattern of the obtained compound was depicted in figure-3.

We Claim:
1. An amorphous solid dispersion of cobicistat, together with one or more pharmaceutical^ acceptable carriers.
2. A process for preparing an amorphous solid dispersion of cobicistat, comprising of the following steps:
a. Dissolving or suspending cobicistat and one or more pharmaceutically acceptable
carriers in a suitable solvent or mixtures thereof; and
b. isolating an amorphous solid dispersion of cobicistat.
3. The process according to claim-2, wherein,
in step-a) the suitable solvent is selected from alcohol solvents, chloro solvents, ester solvents, polar aprotic solvents, ketone solvents, hydrocarbon solvents and polar solvent like water or mixture thereof;
in step-b) isolation may be affected by removing the solvent include filtration, using a rotational distillation device such as a Buchi Rotavapor, spray drying, agitated thin film drying ("ATFD"), freeze drying (lyophilization), and the like or any other suitable technique.
4. The amorphous solid dispersion according to preceding claims, wherein pharmaceutically
acceptable carriers include both polymeric and non-polymeric carriers; hydrophilic and
hydrophobic carriers; cellulose derivatives such as cellulose acetate, cellulose nitrate,
cellulose xanthate, carboxy methyl cellulose, micro crystalline cellulose herein referred as
"MCC" and hydroxy ethyl cellulose and ploymers such as suitable water soluble polymer
is a chemically modified cellulose and/or cellulose ether, and in particular is selected from
the group consisting of alkylcellulose, e.g. propylcellulose; hydroxalkyl cellulose, e.g.
hydroxyethyl cellulose, hydroxyalkylalkylcellulose, e.g. hydroxyethyl methylcellulose
(HEMC), carboxyalkylcellulose, e.g carboxymethyl cellulose (CMC),
carboxymethylhydroxyethylcellulose (CMHEC), hydroxyethyl carboxy methylcellulose
(HECMC), sodium carboxymethylcellulose, cellulose acetate phthalate (CAP), hydroxyl

propylmethylcellulose phthalate (HPMCP) or mixtures thereof; and copovidone; mannitol, lactose, fructose, sorbitol, xylitol, maltodextrin, dextrates, dextrins, lactitol.
5. The amorphous solid dispersion according to preceding claims, wherein pharmaceutically acceptable carrier is used in about 0.1, about 0.5, about 1.0, about 2.0, about 3.0, about 4.0, about 5.0, about 6.0, about 7.0, about 8.0, about 9.0 or about 10.0 portions by weight per one portion by weight of Cobicistat.
6. A process for the preparation of a solid dispersion of cobicistat compound of formula-1 in combination with MCC, comprising of the following steps:
a. Adding dichloromethane to cobicistat,
b. adding micro crystalline cellulose to the reaction mixture,
c. stirring the reaction mixture,
d. distilling off the solvent completely from the reaction mixture to provide a solid
dispersion of cobicistat compound of formula-1 with MCC.