Controlled Release formulations of challenging molecules
A large number of drug substances have low aquepous solubility and/or a narrow window of absorption in the upper GI segment. As a result they show low bioavailability and require large doses to achieve the desired therapeutic benefits. Development of controlled release formulations of such molecules is extremely challenging, but very important from both the therapeutic efficacy and life cycle management viewpoints. Rubicon has developed RubiReten® technology for presenting controlled release formulations of such molecules.
Potential Drug Candidates for RubiReten®
Your Molecule ; Our Technology
Drug substances which exhibit one or more of following properties are potential candidates for RubiReten®
- Low aqueous solubilty
- Narrow absorption window
- Resultant low bioavailability
- High doses and frequent administration
- Significant side effects
- Require site specific delivery in stomach
- Potential for degradation in low GIT regions
RubiReten® technology is based on the concepts of solubilisation and gastric retention.This technology involves treatment of the candidate drug substance with solubility enhancers and its subsequent incorporation into a gastroretentive matrix (GRM) system. This GRM is based on “swelling” and “floating” principles, The key outcomes of this are gastric retention of the dosage form and a slow trickling of the drug in solution across the absorption window, This controlled drug release and maximization of its absorption are achieved. Use of in-vitro evaluation of the in-vivo studies in human volunteers confirmed the performance of this system in terms of gastric retention, controlled release for the drug and increased bioavailability.
The basic technology is protected by patent applications filed in various countries. Additional patent applications have also been filed for expanding the scope of the technology.
- Can achieve controlled drug release and enhanced absorption,where traditional methods fail
- Suitable for drugs having large doses
- Pharmacopoeial and GRAS listed excipients
- Conventional method of manufacture
- Several in-vitro tests developed to confirm the behavior of the dosage form
- Storage stability confirmed
Bioenhanced gastroretentive formulation for once a day of administration Angiotensin Receptor Blocker (ARB)
A bilayer gastroretentive tablet was developed. Solubility of the drug substance was increased using solubilizers and this solubilized form was incorporated into the GRM system. After characterizing the system thoroughly in-vitro with respect to swelling and floating time and drug release, a bioavailability study was conducted to compare the developed formulation (T) with the marketed immediate release tablet formulation in healthy human volunteers in the fed condition.
The results confirmed:
Retention of the formulation in the stomach by the fact that Tmax was increased from 3.0 to 4.8 hrs, and
Controlled drug release and enhanced bioavailability through significantly higher plasma concentrations over a much longer period.
Challenges and achievements
- Retardation and control of drug release
- Prolonged and increased drug absorption
- Bioavailability enhancement