Antidiabetic pharmaceutical compositions and preparation method thereof

An oral dosage form of a pharmaceutical composition for managing diabetes or prediabetes in a subject, comprising:

• a core portion comprising at least one first antidiabetic agent, each at a therapeutically effective amount wherein the at least first antidiabetic agent comprises metformin hydrochloride (metformin HCl);
• an outer portion comprising at least one second antidiabetic agent, each at a therapeutically effective amount;
• and
• a controlled membrane film encapsulating the core portion and sandwiched between the core portion and the outer portion, wherein the controlled membrane film is provided with at least one passageway configured to allow the at least one first antidiabetic agent to release out of the core portion therethrough when the oral dosage form is in an aqueous environment;
• wherein:
• the oral dosage form realizes a controlled release of the at least one first antidiabetic agent such that upon a single-dose oral administration, the oral dosage form provides a maximum plasma concentration of the at least one first antidiabetic agent in the subject from approximately 7.5 to 15 hours after administration;
• when the oral dosage form is test in a USP Type II apparatus at approximately 50 rpm at approximately 37° C. in 900 ml of a medium having a pH of approximately 6.8, the metformin hydrochloride exhibits a dissolution profile such that upon contacting the oral dosage form with the medium:
• Less than 30% of the metformin hydrochloride is released at approximately 2 hours;
• 20-60% of the metformin hydrochloride is released at approximately 4 hours;
• 50-92% of the metformin hydrochloride is released at approximately 8 hours;
• no less than 60% of the metformin hydrochloride is released at approximately 12 hours;
• and
• no less than 80% of the metformin hydrochloride is released at approximately 16 hours.