Claims:We Claim:
1. A pharmaceutical composition, comprising:
a) candesartan cilexetil; and
b) HPMC E5 LV;
wherein the weight ratio of candesartan cilexetil to HPMC E5 LV is in the range of 1:1 to 5.
2. The pharmaceutical composition as claimed in claim 1, wherein the composition is in the form of solid dispersion.
3. A process for preparation of solid dispersion of candesartan cilexetil, comprising:
a) dissolving candesartan cilexetil in ethanol;
b) separately, dissolving HPMC E5 LV in water;
c) mixing solution of step a) and step b) to produce a clear solution;
d) spray drying the mixture of step c) and evaporating solvent using an input temperature of 120°C, an output temperature of 80°C, a feed pump speed of 10 ml per minute, and an aspiration speed of 30% to produce the candesartan cilexetil solid dispersions;
wherein the weight ratio of candesartan cilexetil to HPMC E5 LV is in the range of 1:1 to 5.
Dated this 11th day of January, 2022
To be signed digitally by
(Sanchita Tewari)
Agent for the Applicant
Patent Agent (IN/PA 2711)
, Description:Technical Field of the Invention
The present invention relates to a solid dispersion of candesartan cilexetil and HPMC E5 LV. The present invention also relates to a process for preparing solid dispersion of candesartan cilexetil. The solid dispersion of present invention has improved solubility and dissolution rate for candesartan cilexetil.
Background of the Invention
Lower water solubility of drug formulations is a major problem in drug delivery. Low solubility and dissolution rate of poorly soluble drugs pose problems in absorption of drugs in stomach and intestine, leading to insufficient drug bioavailability. For better dissolution of poorly water-soluble drugs in gastric fluids, increase in the surface area of the drug with high spreading activity is required. Decreasing the particle size of the drugs improves the active surface area of the drugs. Solid dispersion of the drugs shows better results in enhancing the bioavailability and dissolution of drugs (Sharma, D., Soni, M., Kumar, S. and Gupta, G.D., 2009. Solubility enhancement–eminent role in poorly soluble drugs. Research Journal of Pharmacy and Technology, 2(2), pp.220-224). Candesartan cilexetil is an angiotensin II receptor blocker useful for treatment of hypertension. Candesartan cilexetil is a BCS class II drug (low solubility, high permeability) with intrinsic solubility: 0.0595 mg/L and has weak acidic behavior.
However, there is still a need to improve rate of solubilization of candesartan cilexetil.
Objects of the Invention
The main object of the present invention is to provide a solid dispersion of candesartan cilexetil and HPMC E5 LV;
Another object of the invention is to provide a process for preparation of solid dispersion of candesartan cilexetil.
Summary of the Invention
Accordingly, the present invention provides a pharmaceutical composition, comprising candesartan cilexetil and HPMC E5 LV.
In an embodiment, the weight ratio of candesartan cilexetil to HPMC E5 LV is in the range of 1:1 to 5.
In an embodiment, the pharmaceutical composition of present invention is in the form of solid dispersion.
The present invention also provides a process for preparation of solid dispersion of candesartan cilexetil, which comprises, dissolving candesartan cilexetil in ethanol; separately, dissolving HPMC E5 LV in water; mixing above solutions to produce a clear solution; spray drying above mixture and evaporating solvent using an input temperature of 120°C, an output temperature of 80°C, a feed pump speed of 10 ml per minute, and an aspiration speed of 30% to produce the candesartan cilexetil solid dispersions.
In an embodiment, the weight ratio of candesartan cilexetil to HPMC E5 LV is in the range of 1:1 to 5.
Detailed description of the Invention
In accordance with the first object of the present invention, the invention provides a pharmaceutical composition, comprising, candesartan cilexetil and HPMC E5 LV.
The weight ratio of candesartan cilexetil to HPMC E5 LV in the pharmaceutical composition of the present invention is in the range of 1:1 to 5.
The pharmaceutical composition of the present invention is in the form of solid dispersion.
The present invention further provides a process for preparation of solid dispersion of candesartan cilexetil, comprising, dissolving candesartan cilexetil in ethanol; separately, dissolving HPMC E5 LV in water; mixing above solutions to produce a clear solution; spray drying the obtained mixture and evaporating solvent using an input temperature of 120°C, an output temperature of 80°C, a feed pump speed of 10 ml per minute, and an aspiration speed of 30% to produce the candesartan cilexetil solid dispersions.
The weight ratio of candesartan cilexetil to HPMC E5 LV in the solid dispersions of the present invention is in the range of 1:1 to 5.
The solid dispersion of present invention has better solubility than its corresponding physical mixture.
The solid dispersion of present invention has improved dissolution profile.
The solid dispersion of present invention has usefulness in treatment of hypertension.
The solid dispersion of present invention can be used for formulating a suitable dosage form such as granules, beads or tablets.
The solid dispersion of present invention can be mixed with any compatible excipients of the art to obtain suitable dosage form. Exemplary list of suitable ingredients or excipients in the dosage form of present invention includes but are not limited to lactose, corn starch, polyethylene glycol, various cellulose derivatives, magnesium stearate etc.
Suitable granulation method in the art that may produce desired granules for solid dispersion of present invention can be used for producing granules, preferably moist or wet granulation are preferred, for producing granules of solid dispersion of present invention.
The granules or beads obtained can be further compressed using suitable force in a tablet compression machine to form tablets.
The granules or beads can also be filled into an empty gelatin capsule shell to give capsules.
Examples
The following examples are given by way of illustration of the present invention and therefore should not be construed to limit the scope of it.
EXPERIMENT:
Materials:
Candesartan cilexetil was provided by Micro Labs Ltd in India as a gift sample. Dr. Reddy's Laboratory donated HPMC E5 LV (hydroxypropyl methylcellulose). All other reagents, such as ethanol were of analytical grade.
Preparation of physical mixture:
The candesartan cilexetil /HPMC E5 (PM) physical combination was made by utilizing a basic mortar and pestle mixing procedure in various weight-to-weight ratios ranging from 1:1 to 1:5 w/w.
Preparation of Solid Dispersions by Spray Drying:
The solution was prepared by dissolving 500 mg of candesartan cilexetil in 25 ml of ethanol and 2.5 g of HPMC E5 LV in 50 ml of distilled water and mixing both solutions, which produces a clear solution.
The hydroalcoholic solution of candesartan cilexetil and HPMC E5 LV was evaporated in an optimal ratio (1:5 w/w) using a spray dryer to produce the Candesartan cilexetil solid dispersions (LU- 222, Labultima, India). Using an input temperature of 120°C, an output temperature of 80°C, a feed pump speed of 10 ml per minute, and an aspiration speed of 30 %, the solvent was evaporated.