Accor­dion Pill®: Lam­i­nated, folded, encapsulated

So much for cap­sules can only be filled with pow­ders, pel­lets, microtablets or liq­uids! The Accor­dion Pill® by Intec Pharma Ltd. is a drug delivery system that uses active ingre­dient con­taining poly­meric films, which are folded into an undu­lated shape. This system com­bines an effi­cient gas­tric reten­tion and spe­cific release mech­a­nism. The man­u­fac­turing tech­nology for this inno­v­a­tive product was devel­oped in close coop­er­a­tion with Harro Höfliger.

It is a problem that affects mil­lions of patients around the world: After the intake of drugs, the level of active sub­stances rises in the blood, reaches a peak and then sub­sides. To ensure that the level of active ingre­dient in the body is always within the appro­priate con­cen­tra­tion range, it is nec­es­sary to take the med­ica­tion at reg­ular inter­vals. For many patients, how­ever, this poses an enor­mous chal­lenge in coping with their daily rou­tines, and reduces their quality of life. Due to the fluc­tu­a­tion range, the optimal level of active sub­stances is often avail­able for a lim­ited period only. The Israeli enter­prise Intec Pharma has addressed these issues by devel­oping the Accor­dion Pill® platform.

The ­Accor­dion Pill® looks like a normal cap­sule, how­ever, its inte­rior con­tains a small folded GRDF, short for “Gastro Reten­tive Dosage Form”, which con­sists of sev­eral layers of biodegrad­able poly­meric films and the active sub­stance. The Accor­dion Pill® is named after the char­ac­ter­istic folding of the GRDF, which is rem­i­nis­cent of the musical instru­ment. After taking an Accor­dion Pill®, the cap­sule dis­solves in the stomach, the GRDF unfolds and releases the active ingre­dient con­tin­u­ously over a period of eight to twelve hours. This also applies to sub­stances lasting usu­ally for only two to three hours when taken orally.

The Accordion‘s pro­duc­tion is as com­plex as the inno­v­a­tive nature of this dosage form. “Depending on the type of appli­ca­tion, dif­ferent web mate­rials must be lam­i­nated and welded, fol­lowed by punching and folding of the GRDF before it is encap­su­lated,” explains Ronny Rein­berg, Vice Pres­i­dent of Tech­nology Affairs at Intec Pharma.

The Accor­dion Pill® is a unique delivery plat­form based on folded mul­ti­layer films. It pro­vides a ­better treat­ment by improving the phar­ma­co­ki­netics of drugs with narrow absorp­tion win­dows or poor sol­u­bility. Fur­ther­more, it allows fixed-dose com­bi­na­tions. Safety and effi­cacy have been tested in more than 30 clin­ical studies, with tens of thou­sands of administrations.

From manual sta­tions to a state-of-the-art line

Devel­op­ment was equally com­plex. “In the ini­tial stage, we man­u­fac­tured the Accor­dion Pill® in a com­pletely manual pro­cess by using a self-designed folding unit, among other things. It was a long way to today‘s com­pletely auto­mated pro­duc­tion,” says Ronny Reinberg.

“It was a long way to today‘s com­pletely auto­mated pro­duc­tion.” Ronny Rein­berg, Vice Pres­i­dent Tech­nology Affairs at Intec Pharma

In 2013, when Harro Höfliger was com­mis­sioned with the devel­op­ment of a pilot-scale system for the pro­duc­tion of clin­ical sup­plies of the Accor­dion Pill®, the com­pany could draw on the expe­ri­ence gained with the manual sta­tions. “When it comes to com­plex prod­ucts and spe­cial solu­tions such as the ­Accor­dion Pill®, it always makes sense to start with smaller machines in order to acquire pro­duc­tion expe­ri­ence,” explains Frank Erbach, Senior Sales Director at Harro Höfliger. “This is why we designed a PML ver­sion – our small web pro­cessing machine – which was pre­cisely tai­lored to the exper­tise gained with the manual machines.”

In 2017, this was fol­lowed by the order for a high-per­for­mance line. While the web mate­rial on the pilot-scale line was still processed in inter­mit­tent mode and on two lanes, the high-per­for­mance line is oper­ated in con­tin­uous motion on ten tracks and achieves an output of up to 360 prod­ucts per minute. The cen­ter­piece of the line is the PMK, a pro­duc­tion plat­form for web pro­cessing. As with the PML machine, the var­ious GRDF layers are first joined to­gether. Folding sta­tions then fold the GRDFs into a com­pact format before encap­su­la­tion with a Modu‑C machine. The line is com­pleted with the Accura‑C, a cap­sule weighing system for quality assurance.

Ronny Rein­berg is very sat­is­fied with the coop­er­a­tion: “Our Accor­dion Pill® is by no means an ordi­nary product. For this reason, Harro Höfliger car­ried out tests, for example exten­sive proof-of-prin­ciple of the crit­ical sta­tions. Thus, we have jointly suc­ceeded in making the leap from manual machines to pilot-scale equip­ment to high-per­for­mance production.”

About Intec Pharma Ltd.

Intec Pharma Ltd. is a bio­phar­ma­ceu­tical com­pany focused on devel­oping drugs in the clin­ical stage on the basis of its pro­pri­etary Accor­dion Pill® plat­form technology.

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Photos and graphics: Intec Pharma Ltd.