In-situ gel is a type of drug delivery system in which the solution is administered, and the liquid transforms into a semi-solid gel at the site of administration. In recent years, as a highly attractive drug delivery system, in-situ gel formulations have been increasingly recognized in pharmaceutical and biomedical applications.
Classification and Formation Mechanism of In-situ Gels
Depending on the solution-gel phase transition factors that influence the in situ gels in vivo, in situ gels can be classified into four categories: temperature-sensitive, pH-sensitive, ion-sensitive, and in situ polymer precipitation systems, etc.
Figure The transition from solution to gel state in the original gels at different temperatures.
The formation mechanism of in situ gels can be divided into physical and chemical mechanisms. Among them, the physical mechanism includes diffusion and expansion, while the chemical mechanism includes ion crosslinking, enzyme-mediated crosslinking, and photo-crosslinking. The solvents and matrix used in the formation of gels with different mechanisms also differ.
Advantages of In-Situ Gel Injection
In situ gel formulations are in a liquid state, which has a low viscosity that makes it easier to administer. In the gel state, they have a retentive property that controls the slow release of the drug, thereby prolonging the drug's residence time at the designated site, reducing the number of administrations, lowering the therapeutic dose, improving patient compliance, and reducing local and systemic side effects.
Case Studies of In-Situ Gel Injection
To date, a total of 8 in situ gel injectables have been marketed globally, belonging to analgesics, local anesthetics, and psychotropic drugs, etc. The following table shows the formulations of these products:
It can be found that in the injectable in situ gel system, organic solvents are uniformly added, including NMP, ethanol, benzyl alcohol, and dimethyl sulfoxide. The matrix used in the system includes PLGA/PLA, soy phosphatidylcholine, dioleoyl glycerol, triacetin glycerol, and polyprimoleate, among others.
Now, let's share a simple case using Buvidal/Brixadi:
In 2023, Brixadi (the US brand name of Buvidal) was approved by the FDA for the treatment of opioid use disorder (OUD).
Brixadi is the only opioid use disorder treatment currently available in the United States that offers both weekly and monthly injections and personalized dose selection, aligning with current daily dosing guidelines. It is also the only long-acting product that can begin treatment on the first day after an oral buprenorphine trial dose.
Additionally, compared to other products on the US market, Brixadi has the advantages of smaller needle, larger dose, multiple injection sites, and stability at room temperature.
The following is the prescribing information for Brixadi:
Brixadi weekly: Each milliliter of the solution contains 50 mg of active ingredient buprenorphine, as well as 10% anhydrous ethanol, soybean lecithin/dioleoyl glycerol 50:50.
Brixadi Monthly: Each milliliter of the solution contains 356 mg of active ingredient buprenorphine, as well as 30% anhydrous ethanol, soybean lecithin/dioleoyl glycerol 40:60.
Through this issue's introduction, we have gained a basic understanding of the preparation mechanism and formulation components of in situ gels, which are relatively simple, and the in situ gel formulation has the advantages of low dosing frequency, long drug retention time, and high patient compliance.
With the development of future pharmaceutical excipients, safe and accessible injectable excipients will continue to support the development of in situ gel formulations.
AveTech has launched a new product, dihydroxyacetone, to help domestic enterprises develop new in-situ gel formulations!
Product Information
1.Product Name: Dihydroxyacetone
2. English name: Diolein
3. CAS Number: 25637-84-7
4. Molecular Formula: C39H72O5
5. Purity: ≥95%
6. Water: 0.10%
EN
jp 
ko 
fr 
es 
ru 
ms 
id 
bn 
