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Pharmaceutical formulation of 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide

IP.com Disclosure Number: IPCOM000254574D
Publication Date: 2018-Jul-12
Document File: 6 page(s) / 376K

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The IP.com Prior Art Database

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Pharmaceutical formulation of 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-

trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide

Two strenghts of 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-

trifluoroethoxy)phenoxy]ethyl}

amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide were developed, differing in the

quantity of silodosin per unit: 4 mg and 8 mg.

The difference between the strengths is in the size and colour of capsule shells and different

imprint on the surface of capsule shells. These parameters have no effect on quality, safety

and efficiency of the final product.

Properties of reference product

Qualitative composition of Urorec ® hard capsules from the European market are presented in

the table 1 (http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-

_Product_Information/human/001092/WC500074180.pdf).

Table 1. Qualitative composition of Urorec ® hard capsules.

Composition

Silodosin

Starch, pregelatinised (maize)

Mannitol

Magnesium stearate

Sodium laurilsulfate

4 mg strength additionally contain capsule shell size 3, comprising gelatin, titanium dioxide,

E171 and yellow iron oxide, E172.

8 mg strenght additionally contain capsule shell size 0, comprising gelatin and titanium

dioxide, E171.

Urorec ® hard capsules are packed in PVC/PVDC/aluminium foil blisters, packed in cartons.

The shelf life of the product is 3 years. It should not be stored above 30°C.

Table 2. Quantitative composition of Urorec ® hard capsules (in mg/unit).

Ingredient Strenght

4 mg 8 mg

Capsulating mixture

Silodosin 4 8

Starch, pregelatinised (maize) 35 70

Mannitol 132.4 264.8

Magnesium stearate 1.8 3.6

Sodium laurilsulfate 1.8 3.6

Total 175 350

Capsule shell

Gelatine

47.434

98

Titanium dioxide, E171

Ferric oxide yellow, E172

0.48

0.086

2

/

Total 48 100

In 4 mg strenght (Sylodyx 4 mg, B. No. SE4C43), we have confirmed the quantities of:

- starch (20.2 ± 0.5% w/w of capsulating mixture), corresponding to 35 mg per 175 mg

of capsulating mixture,

- mannitol (129 mg),

- sodium laurilsulfate (2.2 mg),

which is in good accordance with the quantities as defined in Table 2.

Furthermore, the polymorphic form of silodosin in reference product is form alpha.

Manufacturing process of the reference product involves standard technology using standard

manufacturing processes such as mixing, granulation, sieving and capsule filling

(http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-

_Public_assessment_report/human/001092/WC500074183.pdf).

Furthermore, the objective in the development was to ensure adequate chemical stability of

the product, develop a robust formulation and an efficient, simple and reproducible

manufacturing process. For this reason, the formulation of hard capsules should possess the

following physical properties to assure optimal technical feasibility and stability of the

formulation:

- flowability,

- compatibility,

- lubricity and

- appearance.

The polymorphic form of 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-

trifluoroet...