DESC:BACKGROUND OF THE INVENTION
Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis refers to illness due to allergy, airway or lung invasion, cutaneous infection, or extra pulmonary dissemination caused by species of Aspergillus (A), most commonly A. fumigatus, A. flavus, and A. terreus. Aspergillosis is a group of diseases which can result from aspergillus infection and includes invasive aspergillosis, allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA) and aspergilloma. It usually affects the respiratory system (windpipe, sinuses and lungs), but it can spread to anywhere in the body.
Depending on a number of factors, the symptoms of aspergillosis can vary in severity from mild wheezing to coughing up blood. Someone with a weakened immune system is at greater risk of being more severely affected. Aspergillosis is caused by breathing in small spores of aspergillus mould.
There are four main types of aspergillosis in the lungs. They are (i) allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS); (ii) chronic pulmonary aspergillosis (CPA), including aspergilloma; (iii) invasive pulmonary aspergillosis (IPA); and (iv) aspergillus bronchitis and tracheobronchitis. There are also a number of other types of aspergillosis, including aspergillus sinusitis, postoperative aspergillosis, and fungal keratitis.
Invasive pulmonary aspergillosis (IPA) usually only affects people with lowered immunity, such as those who have received a bone marrow transplant or cancer treatment, or those with HIV or AIDS. It's the most serious type of aspergillosis.
It's almost impossible to avoid the aspergillus fungus completely, but there are precautions one can take to prevent aspergillosis. The current medical treatments for aggressive invasive Aspergillosis include voriconazole and liposomal amphotericin B in combination with surgical debridement. For the less aggressive allergic bronchopulmonary aspergillosis findings suggest the use of oral steroids for a prolonged period of time, preferably for 6–9 months in allergic aspergillosis of the lungs.
Isavuconazonium sulfate is the prodrug of isavuconazole, an azole antifungal drug. Isavuconazonium sulfate drug substance is an amorphous, white to yellowish-white powder. Chemically, isavuconazonium sulfate is glycine, N-methyl-, [2-[[[1-[1-[(2R,3R)-3-[4-(4-cyanophenyl)-2-thiazolyl]-2-(2,5-difluorophenyl)-2-hydroxybutyl]-4H-1,2,4-triazolium-4-yl]ethoxy]carbonyl]methylamino]-3-pyridinyl]methyl ester, sulfate (1:1) with the following structure:

Isavuconazonium sulfate
Pharmacologic mechanism of action of isavuconazonium is it inhibits the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is responsible for the conversion of lanosterol to ergosterol. An accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane weaken the membrane structure and function.
Isavuconazonium is currently sold in the United States under the trade name Cresemba® by Astellas, in capsules containing 186mg strength and powder for IV (Infusion) containing 372mg of isavuconazonium and is approved for patients 18 years of age and older for the treatment of invasive aspergillosis and invasive mucormycosis.
U.S. Patent No. 6,812,238; 7,189,858; 7,459,561 discloses azolium derivatives which have antifungal activity and are useful for the treatment of fungal diseases.
U.S. Patent No. 6,300,353 discloses a broad group of compounds that includes isavuconazole.
U.S. Patent No. 8,536,208 discloses a pharmaceutical composition for oral administration which is self-emulsifying on contact with an aqueous phase, in particular gastrointestinal fluids, and which comprises: (a) an antifungally active isavuconazole compound or a pharmaceutically acceptable acid addition salt thereof, and (b) a carrier comprising a solubilizer component for the antifungally effective component.
As mentioned above isavuconazonium or pharmaceutically acceptable salt thereof is present in prodrug form, which is very unstable in nature. Hence there still exists an enduring need for an alternative formulation of isavuconazonium or pharmaceutically acceptable salt thereof with stabilizer along with excellent storage stability.
The inventors have overcome various problems occurred in formulating compositions having unstable active ingredient by designing a novel pharmaceutical composition wherein active ingredient is stabilized with the use of stabilizer in the formulation, optionally with or without other pharmaceutically acceptable excipients, so that the active ingredient remains stable in the formulation.
The inventors of the invention have surprisingly found that by using stabilizer in the formulation; along with or without pharmaceutically acceptable excipient, has shown excellent storage stability with drug content uniformity.
Hence it is an object of the invention to provide a novel dosage form, which can provide stable formulation of isavuconazonium with the help of stabilizer and do not posing any stability issues in a pharmaceutical composition or its bioavailability.
The invention also provides process for preparing pharmaceutical compositions comprising pharmaceutically effective amounts of isavuconazonium or pharmaceutically acceptable salt thereof. The compositions of the invention are useful as anti-fungal in the treatment of aspergillosis and mucormycosis.
SUMMARY OF THE INVENTION
In one general aspect, there is provided a pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof.
In another general aspect, there is provided a solid oral pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof.
In another general aspect, there is provided a solid oral pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof, wherein the composition further comprises stabilizer.
In another general aspect, there is provided a solid oral pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof, wherein the composition further comprises stabilizer and optionally use of one or more pharmaceutically acceptable excipient.
In another general aspect, there is provided a solid oral pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof, wherein composition is present in the form of powder, granules, tablet, capsule, solution, suspension, powder for solution.
In another general aspect, there is provided a solid pharmaceutical composition comprising:
a) isavuconazonium or pharmaceutically acceptable salt thereof;
b) one or more stabilizer comprising magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.
In another general aspect, there is provided a pharmaceutical composition, wherein the amount of isavuconazonium or pharmaceutically acceptable salt thereof present in the composition is about 25% w/w to about 75% w/w of the composition.
In another general aspect, there is provided a pharmaceutical composition, wherein the amount of isavuconazonium or pharmaceutically acceptable salt thereof is present in the range of 40 % w/w to 60% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition, wherein the amount of isavuconazonium or pharmaceutically acceptable salt thereof is about 50% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition, wherein the magnesium citrate is present in the range of 5% to 10% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition, wherein the amount of magnesium citrate is about 7% w/w of the composition.

In another general aspect, there is provided a pharmaceutical composition, wherein the ratio of isavuconazonium or pharmaceutically acceptable salt thereof to magnesium citrate is about 1:0.05 to about 1:1

In another general aspect, there is provided a pharmaceutical composition, wherein the ratio of isavuconazonium or pharmaceutically acceptable salt thereof to magnesium citrate is 1:0.14.

In another general aspect, there is provided a pharmaceutical composition, wherein the solid pharmaceutical composition is in immediate release capsule dosage form.

In another general aspect, there is provided a pharmaceutical composition comprising:
a) 40% to 60% w/w of isavuconazonium or pharmaceutically acceptable salt thereof;
b) 5% to 10% w/w of magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a pharmaceutical composition comprising:
a) 186mg of isavuconazonium or pharmaceutically acceptable salt thereof;
b) 26mg of magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a pharmaceutical composition comprising:
a) about 50% of isavuconazonium or pharmaceutically acceptable salt thereof;
b) about 7% of magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.

In another general aspect, there is provided a pharmaceutical composition in the form of capsule dosage form comprising:
a) 186mg of isavuconazonium or pharmaceutically acceptable salt thereof;
b) 26mg of magnesium citrate;
c) 150mg microcrystalline cellulose;
d) 3mg colloidal silicon dioxide;
e) 2mg talc; and
f) 3mg stearic acid

In another general aspect, there is provided a pharmaceutical composition comprising:
a) about 50% of isavuconazonium or pharmaceutically acceptable salt thereof;
b) about 7% of magnesium citrate;
c) about 40% microcrystalline cellulose;
d) about 0.8% colloidal silicon dioxide;
e) about 0.5% talc; and
f) about 0.8% stearic acid
In another general aspect, there is provided a process for preparation of a solid oral pharmaceutical composition, wherein the process comprises steps of:
(a) sifting the isavuconazonium or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) sifting the stabilizer with one or more pharmaceutical excipients;
(c) prelubrication of material obtained in step (a) and (b); and
(d) filling the blend obtained in step (c) to the capsule shell to get final dosage form.
In another general aspect, there is provided a process for preparation of a solid oral pharmaceutical composition, wherein the process comprises steps of:
(a) sifting the isavuconazonium or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) sifting the stabilizer with one or more pharmaceutical excipients;
(c) lubrication/prelubrication of material obtained in step (a) and (b); and
(d) compression of to the blend obtained in step (c) to obtain solid dosage form.
In another general aspect, there is provided a process for preparation of a solid oral pharmaceutical composition, wherein the process comprises steps of:
(a) sifting the isavuconazonium or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) sifting the magnesium citrate with one or more pharmaceutical excipients;
(c) lubrication/prelubrication of material obtained in step (a) and (b); and
(d) compression of to the blend obtained in step (c) to obtain solid dosage form.
In another general aspect, the stable pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof, retains at least 90% w/w of total potency of isavuconazonium or pharmaceutically acceptable salt thereof after storage at 40°C and 75% relative humidity for at least 3 months.
The pharmaceutical composition of the present invention exhibits excellent storage stability over the storage period of at least 6 months at 40°C and 75% relative humidity.
In another general aspect, there is provided a method of treating aspergillosis and mucormycosis in a patient which method comprising administering the pharmaceutical composition as substantially described herein to the patient.
DETAILED DESCRIPTION OF THE INVENTION
The term "isavuconazonium" used throughout the specification refers to not only isavuconazonium per se, but also their other pharmaceutically acceptable salt, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs and pharmaceutically acceptable prodrugs thereof.
The compositions of the invention can be prepared together with at least one pharmaceutically acceptable excipient as an oral, parental, inhalation dosage forms comprising the active agent. The pharmaceutical compositions of the invention can be prepared in different dosage forms comprising tablet; capsule; enterically coated or modified-release tablets; controlled-release tablet, extended-release tablet; delayed-release tablet; slow or fast-release tablet; fast soluble tablet; effervescent tablet; effervescent granule; fast soluble powder mixture; water-soluble powder, tablet, or granule; granule; pellet; mini tablet; micro tablet; granule in capsule; pellet in capsule; mini tablet in capsule; micro tablet in capsule or dry powder mixture to prepare syrup; orodispersible tablet; film tablet or combinations thereof; or in any one of liquid forms such as syrup or suspension.
As used herein, the term "treatment" refers to the medical management of a patient with the intent to cure, ameliorate, stabilize, or prevent a disease, pathological condition, or disorder. This term includes active treatment, that is, treatment directed specifically toward the improvement of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the associated disease, pathological condition, or disorder.
The term "active ingredient" refers to a therapeutically active compound, as well as any prodrugs thereof and pharmaceutically acceptable salt, hydrates and solvates of the compound and the prodrugs of isavuconazonium or pharmaceutically acceptable salt thereof.
As used herein, the term “immediate release” refers to the release of drug within a short time period following administration, e.g., generally within a few minutes to about 1 hour.
Pharmaceutical excipients that can be used in the pharmaceutical composition of the present invention can be selected from a group comprising one or more binding agents (binders), disintegrants, lubricants, one or more diluents, glidants, wetting agents, coating agents, anti-adhesive agents, swelling agent, viscosity enhancing agents, filling agents, drying agents, rate controlling polymer agent, surfactants, cosolvents, acidifier, alkaliser, stabilizing agents, pH regulators, flavouring agent, sweeteners, emulgators, antifoaming agents, antioxidants, protective agents, solvents or solvent combinations, colouring agents and complexing agents or the combinations thereof.
As used herein, the term “stabilizer” is an excipient that improves the stability (e.g., the storage stability) of the pharmaceutical composition. The stabilizer that can be used in the pharmaceutical compositions of the invention can be selected from a group comprising organic acids like citric acid, acetic acid, lactic acid, malic acid, oxalic acid and pharmaceutically acceptable salts thereof. The stabilizer preferably used in the pharmaceutical composition is magnesium citrate.
The disintegrants that can be used in the pharmaceutical compositions of the present invention can be selected from a group comprising carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, microcrystalline cellulose, methyl cellulose, chitosan, starch, sodium starch glycolate or combinations thereof.
The binders that can be used in the pharmaceutical compositions of the invention can be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, maltodextrin, methyl cellulose, povidone, co-povidone, starch or combinations thereof.
The diluents that can be used in the pharmaceutical compositions according to the present invention can be selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, dextrose, fructose, lactitol, lactose, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, mannitol, simethicone, sorbitol, starch and starch derivatives, sodium chloride, sucrose, talc, xylitol or the combinations thereof.
The lubricants that can be used in the pharmaceutical compositions of the invention can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, sodium benzoate, potassium benzoate, sodium lauryl sulphate, talc, stearic acid, zinc stearate or combinations thereof.
The glidants that can be used in the pharmaceutical compositions according to the present invention can be selected from but not limited to colloidal silicon dioxide, calcium silicate, magnesium silicate, silicon hydrogel, magnesium trisilicate, cornstarch, talc and the like or combinations thereof.
In an embodiment, there is provided a composition comprising isavuconazonium or pharmaceutically acceptable salt thereof.
In another embodiment, there is provided a solid oral pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof, wherein composition is present in the form of powder, granules, tablet, capsule, solution, suspension, powder for solution.
In another embodiment, there is provided a pharmaceutical composition comprising:
(a) isavuconazonium or pharmaceutically acceptable salt thereof;
(b) stabilizer; and
(c) optionally one or more pharmaceutical excipients.
In another embodiment, there is provided a pharmaceutical composition comprising:
(a) isavuconazonium or pharmaceutically acceptable salt thereof;
(b) magnesium citrate; and
(c) optionally one or more pharmaceutical excipients.
In another embodiment, there is provided a solid pharmaceutical composition comprising:
a) isavuconazonium or pharmaceutically acceptable salt thereof;
b) one or more stabilizer comprising magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.
In another embodiment, there is provided a pharmaceutical composition, wherein the amount of isavuconazonium or pharmaceutically acceptable salt thereof present in the composition is about 25% w/w to about 75% w/w of the composition.
In another embodiment, there is provided a pharmaceutical composition, wherein the amount of isavuconazonium or pharmaceutically acceptable salt thereof is present in the range of 40 % w/w to 60% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition, wherein the amount of isavuconazonium or pharmaceutically acceptable salt thereof is about 50% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition, wherein the magnesium citrate is present in the range of 5% to 10% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition, wherein the amount of magnesium citrate is about 7% w/w of the composition.

In another embodiment, there is provided a pharmaceutical composition, wherein the ratio of isavuconazonium or pharmaceutically acceptable salt thereof to magnesium citrate is about 1:0.05 to about 1:1

In another embodiment, there is provided a pharmaceutical composition, wherein the ratio of isavuconazonium or pharmaceutically acceptable salt thereof to magnesium citrate is 1:0.14.

In another embodiment, there is provided a pharmaceutical composition, wherein the solid pharmaceutical composition is in immediate release capsule dosage form.

In another embodiment, there is provided a pharmaceutical composition comprising:
a) 40% to 60% w/w of isavuconazonium or pharmaceutically acceptable salt thereof;
b) 5% to 10% w/w of magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.

In another embodiment, there is provided a pharmaceutical composition comprising:
a) 186mg of isavuconazonium or pharmaceutically acceptable salt thereof;
b) 26mg of magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.

In another embodiment, there is provided a pharmaceutical composition comprising:
a) about 50% of isavuconazonium or pharmaceutically acceptable salt thereof;
b) about 7% of magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.

In another embodiment, there is provided a pharmaceutical composition in the form of capsule dosage form comprising:
a) 186mg of isavuconazonium or pharmaceutically acceptable salt thereof;
b) 26mg of magnesium citrate;
c) 150mg microcrystalline cellulose;
d) 3mg colloidal silicon dioxide;
e) 2mg talc; and
f) 3mg stearic acid

In another embodiment, there is provided a pharmaceutical composition comprising:
a) about 50% of isavuconazonium or pharmaceutically acceptable salt thereof;
b) about 7% of magnesium citrate;
c) about 40% microcrystalline cellulose;
d) about 0.8% colloidal silicon dioxide;
e) about 0.5% talc; and
f) about 0.8% stearic acid
In another embodiment, there is provided a process for preparation of a solid oral pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof, wherein the process comprises steps of:
(a) sifting the isavuconazonium or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) sifting the stabilizer with one or more pharmaceutical excipients;
(c) mixing powder obtained in step (a) and step (b); and
(d) filling the blend obtained in step (c) to the capsule shell to get final dosage form.
In another embodiment, there is provided a process for preparation of a solid oral pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof, wherein the process comprises steps of:
(a) sifting the isavuconazonium or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) sifting the magnesium citrate with one or more pharmaceutical excipients;
(c) lubricating the blend obtained in step (b) with one or more pharmaceutical excipients; and
(d) filling the blend obtained in step (c) to the capsule shell to get final dosage form.
In another embodiment, there is provided a process for preparation of a solid oral pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof, wherein the process comprises steps of:
(a) sifting the isavuconazonium or pharmaceutically acceptable salt thereof with one or more pharmaceutical excipients;
(b) sifting the magnesium citrate with one or more pharmaceutical excipients;
(c) lubricating the blend with one or more pharmaceutical excipients;
(d) compression of the blend to get tablet dosage form; and
(e) optionally filling tablet dosage form obtained in step (d) in capsule shell to get capsule dosage form.

The pharmaceutical compositions of the invention may also contain one or more additional formulation ingredients selected from a wide variety of excipients known in the pharmaceutical formulation art. According to the desired properties of the pharmaceutical composition, any number of ingredients may be selected, alone or in combination, based upon their known uses in preparing compositions. Such ingredients include, but are not limited to, diluents, compression aids, glidants, disintegrants, lubricants, flavors, flavor enhancers, sweeteners, and preservatives.
In another embodiment, the stable and reproducible pharmaceutical composition comprising isavuconazonium or pharmaceutically acceptable salt thereof, retains at least 90% w/w of total potency of isavuconazonium or pharmaceutically acceptable salt thereof after storage at 40°C and 75% relative humidity for at least 3 months.
In another embodiment, there is provided a method of treating aspergillosis and mucormycosis in a patient which method comprising administering the pharmaceutical composition as described in the invention.
The invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

In accordance with the present invention formulations are set out below

EXAMPLES
Example 1: Capsule Composition of Isavuconazonium sulphate
Sr. No. Ingredients Grade Quantity (mg/capsule)
1 Isavuconazonium sulfate IH 186.00
2 Magnesium Citrate USNF 20-35
3 Microcrystalline cellulose IP 130-170
4 Colloidal silicon dioxide IP 1-5
5 Talc IP 0.5-4
6 Stearic acid IP 1-5
Total 400-500
7 Empty Hard Gelatin Capsule Size '0' IH 1 Nos.

Manufacturing Procedure:
Isavuconazonium sulfate and microcrystalline cellulose were sifted through sieve 40 on vibro sifter. Magnesium citrate and colloidal silicon dioxide were sifted through sieve 30 on vibro sifter. Talc and stearic acid were sifted through sieve 60 on vibro sifter. Then Isavuconazonium sulfate, microcrystalline cellulose, magnesium citrate and colloidal silicon dioxide were cosifted through sieve 30 on vibro sifter and then prelubricated this material with talc in double cone blender at slow speed for 20 minutes. Then this material was lubricated with stearic acid in double cone blender at slow speed for 5 minutes. Lubricated blend was filled into empty hard gelatin capsule size “0” using capsule filling machine under controlled environmental condition during filling of capsule to 25ºC ± 2ºC / NMT 40% RH.

Example 2: Capsule Composition of Isavuconazonium sulphate
Sr. No. Ingredients Grade Quantity (mg/capsule) Quantity (%w/w)
1 Isavuconazonium sulfate IH 186.00 50.27
2 Magnesium Citrate USNF 26.00 7.027
3 Microcrystalline cellulose IP 150.00 40.54
4 Colloidal silicon dioxide IP 3.00 0.811
5 Talc IP 2.00 0.541
6 Stearic acid IP 3.00 0.811
Total 446 100
7 Empty Hard Gelatin Capsule Size '0' IH 1 Nos.

Manufacturing Procedure: As mentioned for Example-1 above.
,CLAIMS:1. A solid oral pharmaceutical composition comprising:
a) isavuconazonium or pharmaceutically acceptable salt thereof;
b) one or more stabilizer comprising magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.

2. The pharmaceutical composition according to claim 1, wherein the isavuconazonium or pharmaceutically acceptable salt thereof is present in the range of 40 % w/w to 60% w/w of the composition.

3. The pharmaceutical composition according to claim 1, wherein the magnesium citrate is present in the range of 5% to 10% w/w of the composition.

4. The pharmaceutical composition according to claim 1, wherein the solid pharmaceutical composition is in immediate release capsule dosage form.

5. A pharmaceutical composition comprising:
a) 186mg of isavuconazonium or pharmaceutically acceptable salt thereof;
b) 26mg of magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.

6. A pharmaceutical composition comprising:
a) about 50% of isavuconazonium or pharmaceutically acceptable salt thereof;
b) about 7% of magnesium citrate; and
c) one or more pharmaceutically acceptable excipients.

7. A pharmaceutical composition in the form of capsule dosage form comprising:
a) 186mg of isavuconazonium or pharmaceutically acceptable salt thereof;
b) 26mg of magnesium citrate;
c) 150mg microcrystalline cellulose;
d) 3mg colloidal silicon dioxide;
e) 2mg talc; and
f) 3mg stearic acid

8. A pharmaceutical composition comprising:
a) about 50% of isavuconazonium or pharmaceutically acceptable salt thereof;
b) about 7% of magnesium citrate;
c) about 40% microcrystalline cellulose;
d) about 0.8% colloidal silicon dioxide;
e) about 0.5% talc; and
f) about 0.8% stearic acid