Technology name
Last update: Oct 2024In-situ Microimplants
Developer(s)
Sponsor(s)
Not specified
Type of technology
Polymer-based in-situ implant
Administration route
Intramuscular
Development state and regulatory approval
Risperidone
Phase III
Approved by the EMA under the brand name OKEDI on 14/02/2022 and approved by the FDA under the brand name RISVAN on 02 April 2024.
Description
Insitu implant (ISM) technology addresses common limitations associated with traditional prolonged-release oral and injectable formulations. This innovative approach utilizes a solid, biodegradable polymer composed of L-lactide and glycolide monomers. By employing a polymeric matrix, ISM addresses several critical limitations, including complex administration procedures, low encapsulation efficiency, and compromised stability of active substances. Furthermore, this technology enables precise control over the initial release of the drug, resulting in consistent therapeutic efficacy.
Developer(s)
ROVI
Laboratorios Farmacéuticos ROVI, founded in 1946 in Madrid, Spain, is a prominent global player in the pharmaceutical industry. Initially established as a domestic company, ROVI has evolved into an international leader in the research, development, manufacturing, and commercialization of both small molecules and biologics using in situ microimplants.
Technology highlight
The in situ implant is a monthly intramuscular injectable no-particulate solid implant composed of a biodegradable copolymer matrix of dimethylaminomethacrylate and other acrylate monomers, exhibiting enhanced encapsulation efficiency and improved stability of the API. The molecular weight of the copolymers exceeds 15 kDa, contributing to the controlled degradation and release profile. Upon injection, the formulation forms a solid depot at the site, enabling the gradual and sustained drug release over several weeks to months. The API particles are maintained within a size range of 10 to 225 microns, optimizing the balance between immediate and sustained release kinetics.
Illustration(s)
Technology main components
(i) Biocompatible polymer ( Copolymer of poly ( lactic acid ) and poly ( lactic acid - co - glycolic acid ) (ii) Water miscible solvent ( Dipole moment is in between 3.5-4.5D) (iii) API dissolved in a miscible solvent
The price of OKEDI (Risperidone ISM) is £222.64/vial in the United Kingdom and its equivalent in EU states.
Safety, Efficacy and Evidence Summary
Phase I studies of Risperidone ISM demonstrated that the most frequent adverse event was hyperprolactinemia, occurring in 54% of participants. A total of 13 serious adverse events (SAEs) were reported, including dystonia.
Not provided
Not provided
Not provided
APIs compatibility profile
Min: 1
Max: 2
Unit: mg/mL
Drug hereby includes the API and/or a metabolite or a prodrug thereof
Targeted drugs for ISM formulation are water-soluble antipsychotic drugs including but not limited to paliperidone, risperidone, olanzapine, opioids like fentanyl, and aromatase inhibitors including but not limited to letrozole and anastrozole.
The water-miscible solvent utilized for dissolving the active pharmaceutical ingredient (API) should exhibit a dipole moment in the range of approximately 3.7 to 4.5 Debye (D) and a dielectric constant between 30 and 50.
The viscosity of the ISM is targeted to fall within the range of 0.50 to 4.0 Pascal-seconds (Pa·s).
30-50 wt%
1 single API :
Min: -1
Max: 3
Only hydrophilic and partial hydrophilic drugs are suitable
Scale-up and manufacturing prospects
ROVI Farmaceuticos has expanded its injectable manufacturing capacity with three new plants, producing 250 million syringes and 160 million vials annually.
Not provided
ISM manufacturing unit is in accordance with ISO 140001:2015 for the production of pharmaceutical specialties and health products in low-volume injectable forms and suppositories. The manufacturing process for these products involves the following steps: 1) Mixing lactic acid and glycolic acid monomeric polymers at a range from 48:52 to 100:0. 2) Mixing the mixture with API dissolved in a water-miscible solvent. 3) Expose the mixture to Beta-radiation (5 - 23 KGy). 4) Sterilize the solvent by filtering it through a medium having a pore size of 0.22 microns or less. 5) Reconstitution process.
Not provided
Excipients & delivery device(s)
No proprietary excipient used
No novel excipient or existing excipient used
No residual solvent used
No delivery device
Additional features
- Biodegradable
- Drug-eluting
- Monolithic
- Removable
- At least 1 year shelf life
- Needs insertion kit
ISM provides a sustained release of API and achieves therapeutic plasma levels within the first day after a single dose of API. The ISM provides a sustained release throughout the 4-week dosing period over multiple intramuscular injections.
Intramuscular ISM injections are prefilled injections with 20G and 21G needles. The injection kit contains a powder-prefilled syringe, a solvent-prefilled syringe, and two sterile safety hypodermic needles: a 20G needle (for gluteus muscle) and a 21G needle (deltoid muscle). Phase I studies revealed a 15% incidence of injection site erythema and a 7.5% incidence of injection site induration, which healthcare professionals should carefully consider.
The ISM has a non-degradable/ non-erodible that provides structural stability for the device regardless of the pH of a surrounding aqueous environment.
Not provided
Therapeutic area(s)
- Oncology : "breast cancer"
- Mental Health Disorders (incl. schizophrenia, bipolar disorders, Schiz. Aff. Dis.) : "schizophrenia"
Not provided
Potential associated API(s)
- Paliperidone
- Risperidone
- letrozole
Use of technology
- Administered by a community health worker
- Administered by a nurse
- Administered by a specialty health worker
Weekly, Monthly
Targeted user groups
- Adults
- Older Adults
- All
Unspecified
Unspecified
No
Not provided
Type D2 Dopamine receptor antagonist
Pre-clinical
Not provided
Schizophrenia
Not provided
Not provided
Not provided
alpha-1 (α1), alpha-2 (α2), and histamine (H1) receptor antagonist
Phase III
Schizophrenia
18-65 aged adults with Schizophrenia
Once monthly
Approved by the EMA under the brand name OKEDI on 14/02/2022 and approved by the FDA under the brand name RISVAN on 02 April 2024.
letrozole
Aromatase Inhibitors
Phase I
Not provided
Breast Cancer
Post Menopausal women
Not provided
Not provided
Procedure for the filling of solids in pharmaceutical containers and the sealing thereof under sterile conditions
A sterile procedure for the filing of solids into pharmaceutical containers and the sealing thereof under sterile conditions is provided. Exemplary containers include syringes, vials, capsules, ampoules, single-dose devices or cartridges. The containers can be filled with powder, granules, nanoparticles or microparticles. After sealing, the containers are airtight. More specifically, the procedure minimizes adherence of those solids to the interior surfaces of the containers during the filling and sealing steps, thus ensuring airtightness of the seal and precision of the weight of the solid dispensed into the containers.
US11987410B2
Not provided
Laboratorios Farmaceuticos Rovi SA
Not provided
May 23, 2040
Active
Injectable composition with aromatase inhibitor
The present invention provides a composition suitable for forming an intramuscular implant. It comprises a biodegradable thermoplastic polymer of polylactic acid (PLA), DMSO and an aromatase inhibitor compound. The invention also provides a kit suitable for the in situ formation of the composition and its use as a medicine for treating cancer, especially breast cancer.
US11918682B2
Composition of the formulation
Laboratorios Farmaceuticos Rovi SA
Not provided
April 16, 2032
Active
Antipsychotic injectable depot composition
The present invention is directed to a composition that can be used to deliver an antipsychotic drug such as risperidone as an injectable in-situ forming biodegradable implant for extended release providing therapeutic plasma levels from the first day. The composition is in the form of drug suspension on a biodegradable and biocompatible copolymer or copolymers solution using water miscible solvents that is administered in liquid form. Once the composition contacts the body fluids, the polymer matrix hardens retaining the drug, forming a solid or semisolid implant that releases the drug in a continuous manner. Therapeutic plasma levels of the drug can be achieved since the first day up to at least 14 days or more even up to at least four weeks.
US10182982B2
Composition of the formulation
Laboratorios Farmaceuticos Rovi SA
Not provided
May 31, 2031
Active
Risperidone or paliperidone implant formulation
The present invention is directed to an injectable intramuscular depot composition suitable for forming an in situ solid implant in a body, comprising a drug which is risperidone and/or paliperidone or any pharmaceutically acceptable salt thereof in any combination, a biocompatible copolymer based on lactic and glycolic acid having a monomer ratio of lactic to glycolic acid of about 50:50 and DMSO solvent, wherein the composition releases the drug with an immediate onset of action and continuously for at least 4 weeks and wherein the composition has a pharmacokinetic profile in vivo that makes it suitable to be administered each 4 weeks or even longer periods.
US11007139B2
Formulation
Laboratorios Farmaceuticos Rovi SA
Not provided
May 31, 2031
Active
Methods for the Preparation of Injectable Depot Compositions
Injectable depot compositions, comprising a biocompatible polymer which is a polymer or copolymer based on lactic acid and/or lactic acid plus glycolic acid having a monomer ratio of lactic to glycolic acid in the range from 48:52 to 100:0, a water-miscible solvent having a dipole moment of about 3.7-4.5 D and a dielectric constant of between 30 and 50, and a drug, were found suitable for forming in-situ biodegradable implants which can evoke therapeutic drug plasma levels from the first day and for at least 14 days.
US20180318208A1
Not provided
Laboratorios Farmaceuticos Rovi SA
Not provided
May 31, 2024
Active
All sponsors
No sponsor indicated