Case Study 1: Colpermin®

Commercial Manufacturing Process

Colpermin® capsules are commercially manufactured in two-piece hard-shell gelatine capsules exclusively by Tillotts Services using our liquid-fill encapsulation technology. Prior to the filling process, the formulation mixture is heated and agitated which produces a liquid form, however once injected into the capsule it cools and sets as a semi-solid gel. The capsules are then sealed with the characteristic blue band which also acts as a tamper proof mechanism.

Each Colpermin® capsule contains 187.2 mg (0.2 ml) of Peppermint oil within an oleo-gelformulation that provides a sustained delivery over 12-14 hours. Our Swissmedic approved GMP manufacturing facility, located near Basel, Switzerland produces over 150 million liquid-filled capsules per year and we can offer integrated formulation development as well as commercial scale manufacturing for global products. Our formulation development and drug delivery teams are supported by well equipped analytical, QA and QC functions.

How it Works

Colpermin® capsules are enterically coated in order to release the active ingredient in the upper part of the ileum. The enteric coating offers some key benefits that include:

The active ingredient, Peppermint oil is accurately delivered to its site of action. If it were not enterically coated most of the Peppermint oil would be absorbed in the proximal small intestine and metabolised.

It removes the risk of drug release in the upper GI tract that could cause local irritation and relaxation of the oesophageal sphincter which can cause oesophageal reflux.

Colpermin® is the Gold Standard liquid-fill, hard-shell capsule product and is also one of the largest in terms of global production volume. It’s targeted delivery to its site of action in the distal small intestine and colon is achieved through its enteric coat that is applied to the capsule after filling and banding. Colpermin® has a novel oleo-gel formulation that provides an optimal and sustained release of the active at the site of action.

Key Product Features

Colpermin® capsules contain 187 mg (0.2 ml) Peppermint oil.

Oleo-gel formulation – ensures sustained delivery (12 - 14 hrs).

Enteric coated, hard-shell capsule – avoids release in the stomach.

Optimal delivery profile for prolonged & effective relief of IBS symptoms.

Global Colpermin® supply is manufactured in Switzerland at Tillotts Services GMP production facility.

Targeted Drug Delivery

Our novel enteric coating technology enables the Colpermin® capsule to survive the acid environment of the stomach and disintegrate only in the less acidic environment of the ileum at a pH of 6.8 or higher (Figure 1). The Colpermin® oleo-gel formulation provides an optimal delivery profile of the active ingredient. Pharmacokinetic studies show that the Peppermint oil is available from 12 to 14 hours after the administration of Colpermin®.

Calcium ions(-)-Menthol

(-)-Menthol

Phospholipid Bilayer L-typeCalciumChannel

ReceptorBinding Site

Mechanism of Action

Colpermin® relieves the painful bowel cramps and bloating associated with Irritable Bowel Syndrome. (-)-Menthol is a major constituent of Peppermint oil which exhibits powerful anti-spasmodic effects. These result from the inhibition of calcium channels in the intestinal smooth muscle cells (Figure 2).

Colpermin® Pharmacokinetic Profile.

Dru

g Re

leas

eCo

ncen

trat

ion

100

<6.5 6.8 >7.0

Delayed Sustained

Stomach ColonDistal Small Intestine

0

0 12

pH Range

ReleaseProfile

GI Area

Time (hrs)

Figure 1. Colpermin® Pharmacokinetic Profile

Figure 2. Anti-spasmodic Effect of (-)-Menthol

For further information on how Tillotts Services can help with your formulation development options, clinical drug product supply or commercial liquid-fill manufacture, please contact us at: E: services@tillotts.com or W: www.tillotts.com

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