spacer
home > pmps > spring 2011 > maximising effectiveness of dpi capsules
PUBLICATIONS
Pharmaceutical Manufacturing and Packing Sourcer

Maximising Effectiveness of DPI Capsules

David Edwards, Capsugel and James Johnston, Aptuit

Industry Requirements

Finding efficient drug delivery methods is becoming increasingly important as the pharmaceutical industry looks to improve the performance of its new compounds and extend the applications of existing drugs. One option that has long been used to successfully treat respiratory conditions and provide compounds with a fast-acting route into circulation is drug delivery via inhalation using a dry powder inhaler (DPI). The two-piece capsule is commonly used to contain a drug dose in a DPI, and Capsugel’s Xcelodose® precision powder micro-dosing system, with its unique method of dosing capsules for R&D, is being routinely chosen by pharmaceutical and biotech firms to automate filling of DPI capsules.

Automatically filling DPI capsules requires equipment that can dose powders without compaction, as it is essential that powder particles freely de-aggregate when the DPI is used. Filling systems must also be able to dose at low weights, while also ensuring the amount of powder in the capsule is precise and reproducible. The system needs to be easily sanitised and work accurately in temperature- and moisturecontrolled environments – another important step in preventing powder aggregation so it flows freely in the capsule. Finally, during the early stages of drug development, high dose flexibility is needed with limited process development. Traditionally, automated methods of dosing capsules have relied on producing a powder plug to fill the capsule. However, this can cause powder compaction, and though traditional automated filling technologies generally dose accurately in the 10 to 40 mg range (the dose range of many new drug formulations for use in DPIs), they are set up to manufacture larger batches. Unfortunately, their operation usually requires a minimum amount of bulk product which is often not available in the early stages of development.

Technology

The Xcelodose® 600S and Xcelodose® 120S systems can rapidly fill high-quality DPI capsules for many forms of inhaled drugs. The Xcelodose® system works on the ‘pepper pot’principle, dispensing a uniform amount of powder each time according to the number of times the pot is agitated and the size of the holes in the pot, without compacting the powder in the capsule.

The Xcelodose® system has a dispensing head that contains a mesh of holes with precise diameters. The dispense head is filled with powder, and with the aid of tapping the powder passes through the mesh via gravity directly into a capsule shell. The capsule base is placed on a seven place microbalance, tared to zero, and dispensing begins. After each discreet dispensing event, the powder forms ‘micro-bridges’ and is not released from the head unless it is tapped again. The amount of powder dispensed is a function of particle size and flow properties of the drug formulation, the size and number of holes in the dispensing head, and the number of taps the dispensing head receives. The weight being dispensed is monitored several times per second during the fill process and the number of taps is adjusted accordingly. When the capsule has reached its target fill weight, the motion stops and the final fill weight is logged by the control system, allowing full traceability of the capsules. The capsule is then automatically moved and replaced by an empty capsule on the microbalance, while the filled capsule is sealed and sorted into an ‘acceptable weight’ bin, or a reject bin if it is out of the set weight range.

Using an Xcelodose® system, high quality capsules made of either gelatin or Hydroxypropyl Methylcellulose (HPMC), such as Capsugel’s Vcaps® Plus capsules, can be accurately dosed with powder weights as low as 0.1 mg and up to several hundred milligrams, in capsule sizes from 000 to 5. The RSD of the Xcelodose® system is around two per cent and it can dose up to 600 capsules per hour. The system can also be fitted with an Xcelodose® system RH control unit which controls the relative humidity to levels as low as five per cent with a tolerance of +/- 1 per cent. This helps prevent hygroscopic compounds from absorbing moisture during dosing, making powders less likely to form aggregates and more likely to remain free flowing in the capsule.

Benefits of the Xcelodose® System for Dosing DPI Capsules

The Xcelodose® system’s ability to accurately dose very small amounts of expensive or potent active pharmaceutical ingredients (APIs) without compaction makes it ideal for dosing DPI capsules during product development – helping to ensure the free flow of powders, increase the dose percentage emitted, and saving money. The Xcelodose® system can also be easily cleaned with all the parts being able to be quickly removed and sanitised prior to the next day’s run. The system can also be kept clean during runs with operators being able to access and swab all the machine parts and clean the dispense heads with isopropyl alcohol (IPA).



Application

Two Xcelodose® systems, an Xcelodose® 600 and an Xcelodose® 600S, are being used at the major drug development services company, Aptuit, to routinely dose HPMC capsules for use in DPIs. Since 2002, Aptuit has used the Xcelodose® system to produce extensive campaigns of DPI capsules for use in clinical phases f or several pharma and biotech clients, sometimes producing as many as 80,000 capsules in a batch.

After assessing a variety of tamp and dosator technologies, Aptuit chose the Xcelodose® systems for automatically filling DPI capsules, primarily because of the system’s ability to dose capsules without compressing the powders inside. The company has filled DPI capsules with 10 to 40mg of approximately eight different blended formulations or spray dried powders for use in respiratory DPIs. Operators at Aptuit prefer to dose blended or spray dried formulations using the Xcelodose® system as its method of loose filling minimises the risk of aggregation – a critical feature to ensure optimum clinical performance of DPI capsules. To date, they have observed no segregation of the components of the blend that has prevented GMP manufacturing. Typical production rates for DPI capsules at Aptuit are 300 to 400 capsules per hour with their Xcelodose® 600S system and 200 to 300 capsules per hour with their Xcelodose® 600 system.

The Xcelodose® system is ideally suited for accelerating production of high-quality capsules for DPIs as Aptuit’s sustained use of the technology for many different clients’ inhaled drug formulations clearly demonstrates.


Read full article from PDF >>

Rate this article You must be a member of the site to make a vote.  
Average rating:
0
     

There are no comments in regards to this article.

spacer

Print this page
Send to a friend
Privacy statement
News and Press Releases

Drive for generics sees Korea increasingly attractive to international pharma

Amsterdam, 31st July 2019: Already home to more than 40 pharmaceutical multinationals, Korea is on course to become a global biotech and pharmaceutical hub by 2025, driven by the surge of international partnerships, biosimilars, an expansion in the export of finished formulations and a robust generics market.
More info >>

White Papers

The Importance of Critical Temperatures in the Freeze Drying of Pharmaceutical Products

Biopharma Group

Every formulation has a critical temperature, below which it should be cooled for complete solidification and maintained below during primary drying in order to prevent processing defects. To design a freeze drying cycle on a rational basis such information should be identified.
More info >>

 
Industry Events

FlyPharma Europe

22-23 October 2019, Copenhagen, Denmark

The FlyPharma Conference Europe 2019 is aimed at forward-thinking individuals and businesses that are ready to uncover the potential in their pharma supply chain. The event offers an interactive platform to discuss current and future challenges within pharma and cargo, with topics including market trends, cold chain innovations, latest regulatory demands, security technology, and how to encourage collaboration between supply chain players. There will be plenty of networking opportunities, including a complimentary evening networking event, where delegates can meet and catch up with senior and executive pharma and cargo professionals – gaining strong, new industry contacts and building on existing ones.
More info >>

 

 

©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement