PDG Technology
Pneumatic dry granulation
The pneumatic dry granulation process is a new and patent-pending technology. The granulation process is based on the use of roller compaction with very low compaction force together with a proprietary air classification method. The method enables production of granules with extraordinary combination of flowability and compressibility.With the technology, it is possible to formulate virtually any pharmaceutical solid dosage product with our dry granulation method as long as the substance itself is somewhat compactable. The technology is also capable of combining two or more compounds into a single tablet for fixed solid-dosage combinations. These new formulations can be patent protected due to the novelty of the manufacturing process.
The pneumatic dry granulation process, together with a set of well-known GRAS excipients, provides a solid platform for rapid product development. The platform minimizes the formulation design time and resource requirements.
PDG Technology™ is the optimal way to find solutions for solid dosage forms as compared to today's standard manufacturing methods:
--Wet granulation--
--- --Roller compaction-
-
--- --Direct compression--
PDG Technology™ has a number of advantages to support the above claims including the following:
- Good granulation results even at high drug loading have been achieved even with materials known to be difficult to handle,
- Higher throughput and lower costs as compared to wet granulation,
- Scale-up is not an issue (since the equipment for development and production is the same,
- The granules and tablets produced show fast disintegration properties, offering the potential for fast release dosage forms,
- Release time can be tailored to requirements,
- The system is closed offering safety advantages due to low dust levels and potential for sterile production or handling of toxic materials,
- The end products are very stable - shelf life may be enhanced, and
- Little or no waste of material.
Due to the high drug loading, galenic developer have more opportunities to enhance the formulations. For example, a tablet with the same weight can contain increased amount of taste masking agent or other excipients.
PDG Technology - a valid alternative to wet granulation
Today, wet granulation is the most commonly used granulation method. Formulation teams will usually target a direct compression or dry granulation formulation whenever possible but in the vast majority of cases (ca. 70%) they end up with a wet granulation formulation due to processing issues.Compared to the PDG Technology™, wet granulation is complex and difficult to control. Wet granulation is also unsuitable for moisture sensitive and heat sensitive drugs, it is more expensive than dry granulation (energy consumption, floor space needs, operator costs, solvent costs and can take a long time).There are a large number of process steps and each step requires qualification, cleaning, and cleaning validation. High material losses can be incurred because of the transfer between stages and there is the ne e d for long drying times.
Scale up is usually an issue, and there are considerable capital requirements. PDG Technology™ solves the above problems.
| Wet Granulation Technologies | PDG Technology™ |
| Small amount of water might introduce problems during manufacturing (hydrolysis) | No problems with moisture sensitive drugs during manufacturing. Shelf life may be enhanced (moisture sensitive drugs) |
| Unsuitable for heat labile drugs | Suitable for heat labile drugs |
| More expensive than dry granulation e.g. energy consumption, floor space, operator costs, cost of solvents | Lower cost of manufacturing compared with wet granulation e.g. energy consumption of PDG ca. 3% of wet granulation |
| Complex processing - rather poor knowledge (HSM) of what happens during agglomeration, more steps needed and many parameters also leading to higher batch-to-batch variations (risk to discard), difficult to control with respect to when to stop for achieving the same properties | Simple processing - 3 steps and only few parameters |
| Scale up usually is an issue - "transportability between the scales is the key", also from one equipment manufacturer to another | Scale-up is relatively straightforward |
| The need for long drying times and associated issues | Fast process |
PDG Technology extends dry granulation
The PDG Technology ™ extends the u se of dry granulation i.e. roller compaction into new areas. In a stand ard roller compaction process, a formulation typically fails due to two reasons: 1) the compactability of the roller compacted mass is not sufficient for tabletting, or 2) the flowability of th e mass is not good enough due to large amount of fines.The standard solution to the flowability problem is the use of vibrating screens, which on the other hand require hard granules. With some substances, hard granules can be produced by increasing the compaction force of the roller compactor. The improved flowability introduces the compactability problem because t he use of high compaction force destroys the compactability.
PDG Technology™ is a unique solution because it enables both flowability and compactability.
| Dry Granulation with Roller Compaction | PDG Technology™ |
| Suitable for a less limited set of materials | Applicable to almost any pharmaceutical material |
| Medium drug-loads (< 50%) can be achieved (depending on re-compactibility) | High drug load (70% - 95%) |
| Lowforce roller compacted material often does not flow easily because it contains a large amount of fine particles | Excellent flow properties |
| Hard granules (made with high force roller compaction) usually have poor tableting properties | Soft and porous granules have good tableting propertie |
Suitable for a limited set of excipients |
Formulations have been developed with standard GRAS excipients |
PDG Technology™ is cost-efficient alternative to direct compression
Direct compression is the most straight-forward manufacturing technology. API is simply mixed with direct compression excipient and pressed to tablets. Both the development and manufacturing are very fast.The disadvantage of direct compression is that the drug loads are low, only up to 20%. Therefore, the set of suitable products is limited. The direct compression excipients are typically more expensive than the PDG Technology™ excipients. Also, the content uniformity is difficult to guarantee, due to completely different flowability characteristics of the API and the direct compression excipients.
PDG Technology™ has only one additional step compared to the direct compression but the advantages of the technology makes the direct compression less attractive also in the production of low drug-loading tablets.
| Direct compression | PDG Technology™ |
| Suitable for a limited set of materials | Applicable to almost any pharmaceutical material |
| Low (< 20%) drug-loads can be achieved |
High (70% - 95%) drug load |
| Segregation issues (due to differences in particle size and bulk density between excipients and the active ingredient) | Excellent flow properties |
| Often poor compressibility, poor flow | Soft and porous granules have good tableting properties |
| Special excipients needed for direct compression are expensive | Formulations have been developed with standard GRAS excipients |
