Topical formulation of high concentration of cationic-form lidocaine hydrochloride with anionic rheology modifers – Interview with Benjamin Gavinet

Benjamin Gavinet did an interesting presentation at the APGI Skin and Formulation conference in Nantes at the beginning of October. We did a small interview with him summarizing the most important topics and results of his presentation.

Pharma Excipients: Hi Benjamin, you did a presentation with the title “Topical formulation of high concentration of cationic-form lidocaine hydrochloride with anionic rheology modifiers” at the Skin and Formulation symposium on October 3rd. Let me ask you some questions about your presentation for all people interested in pharmaceutical excipients.

Benjamin: Hi Markus, sure. I am happy to present some topics out of my presentation and answer your questions.

Pharma Excipients : What was the main purpose of your study?

Benjamin: APIs in their ionized forms are often difficult to deal with as they disrupt polymeric networks. We wanted to provide solutions for formulation of high concentrations of such APIs in thick and stable oil-in-water dosage forms.

Pharma Excipients: Your API choice was lidocaine hydrochloride? Why did you choose this API? Which specific aspects are relevant here?

Benjamin: Lidocaine hydrochloride is a great example of ionic API, as it is completely dissociated once in solution. Another challenge is that Lidocaine is a cationic API, which can lead to incompatibilities with anionic excipients. And we know there is a need on the market for high-strength formulation of Lidocaine, especially for pain management of chronic wounds.

Pharma Excipients: Which excipient you used for your study, what are its characteristics and what makes this excipient specifically suitable for this kind of formulation?

Benjamin: We started with Sepineo™ P 600 (Acrylamide / Sodium acryloyldimethyl taurate copolymer in inverse emulsion) as this polymer is stable at acid pH (addition of Lidocaine HCl leading to pH below 4) and able to stabilize oils even without surfactant addition. However, for formulation of more than 5% of Lidocaine HCl, we had to switch to Sepineo™ PHD 100 (Polyacrylate Crosspolymer-6) which has a more resilient polymeric network.

Pharma Excipients: Understood. Can you shortly describe the various formulation steps and obstacles on your way to the final formulation?

Benjamin: We previously worked with the non-dissociated form of Lidocaine, also known as Lidocaine base. With Sepineo™ P 600, it was very easy to formulate this lipophilic API. However, with Lidocaine HCl it was a completely different story. The main obstacle was to compensate for the loss of viscosity and stability induced by the addition of Lidocaine HCl.

“…even with our polymers being anionic excipients there has been no incompatibilities with the cationic form of Lidocaine…”

Pharma Excipients: Thanks for the process overview. Which step was the most important one? And is there a step/an element you are specifically proud of?

Benjamin: After several trials, we managed to have stable formulation of Lidocaine HCl with satisfying viscosity by increasing the concentration of Sepineo™ P 600. But when formulating 5% of Lidocaine HCl, we reached a limit as the stability was achieved only by using the maximum recommended dose of Sepineo™ P 600. Only by using Sepineo™ PHD 100 were we able to reach the stabilization of 10% Lidocaine HCl, which is a tremendous performance! This really demonstrates the interest of this new polymer for the formulation of stressful APIs and API combinations.

Pharma Excipients: What are the conclusions of your study?

Benjamin: Despite the disruption caused by ionic APIs, there is still room to formulate by choosing the right polymer. Another really interesting point is even with our polymers being anionic excipients there has been no incompatibilities with the cationic form of Lidocaine, as evidenced by the follow-up of API content over a 1-year period.

Pharma Excipients: Thanks a lot Benjamin!Where can people contact you to know more about the study?

Benjamin: Sure, either at my email address [email protected]
or you send an email at [email protected]

Pharma Excipients: Thanks a lot Benjamin for your time and the interesting interview!

Benjamin Gavinet is a topical formulation scientist at Seppic