Orally Disintegrating Tablets: The Effect of Recent FDA Guidance on ODT Technologies and Applications - Pharmaceutical Technology

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Orally Disintegrating Tablets: The Effect of Recent FDA Guidance on ODT Technologies and Applications
The authors describe the various available technologies used in orally disintegrating tablets.

Pharmaceutical Technology

The product is dosed and dried in an all-aluminum blister pack, which offers good physical and environmental protection. The product slightly adheres to the pack, resulting in minimum movement of the product within the blister pockets to ensure robustness during transportation. The product is a wafer-like structure but of minimum friability and of sufficient strength to be removed from the packaging without breakage.

The wafer-like structure and high porosity of Zydis formulations reflect the fact that water is typically the major component of the dosing formulation, so that the weight of the dried product is significantly reduced and often dictated primarily by the dose of the API. The recommended 500-mg weight limit for ODTs is only likely to be approached for the very highest doses in Zydis formulations, and would be offset by the rapid disintegration. The generally low-excipient load is also advantageous for pediatric formulations.

Following administration and rapid dispersion on the tongue, the Zydis formulation effectively reverts to the original API solution/suspension. Therefore, the Zydis ODT provides all the convenience of a solid oral-dose form with the advantages of a solution/suspension product.

The Zydis product has found wide applicability to achieve a range of clinical applications such as:
  • Products bioequivalent to conventional tablets
  • Products suitable for pregastric (buccal and sublingual) uptake to enhance bioavailability and avoid first-pass metabolism, thereby minimizing undesirable metabolites
  • Stable protein and peptide products
  • Vehicles suitable for the delivery of oral vaccines
  • Physical and chemically stable products with shelf life comparable to conventional tablets approximately two to five years.

Quicksolv. The Quicksolv technology (Janssen, a subsidiary of Johnson & Johnson, New Brunswick, NJ) process is similar to the Zydis technology in that an aqueous dispersion of the API and matrix components is first formed and then frozen. Water removal from the frozen matrix can be performed either by lyophilization or submerging frozen product in alcohol (solvent extraction) to produce a dry unit (7). The product formed has uniform porosity and adequate strength for handling. The product has similar properties to that of the Zydis product (7).

Lyoc. The Lyoc process differs slightly in that an oil-in-water emulsion is prepared and placed directly into blister cavities followed by freeze-drying. To maintain homogeneity during freeze-drying, it is necessary to include polymers to increase the viscosity of the matrix to an almost paste-like consistency to prevent sedimentation. The increased viscosity of the matrix reduces the porosity of the product, thereby increasing freeze drying times and having a negative impact on disintegration.

Compressed tablets

The basis for compressed tablet ODTs is the use of super disintegrants, effervescent agents, or high aqueous soluble ingredients or combinations of each.

Orasolv. CIMA Labs' (a subsidiary of Cephalon, Frazer, PA) OraSolv product combines taste-masked active drug ingredients with a low-effervescence system. On contact with saliva, the effervescent system promotes disintegration of the tablet. The OraSolv process typically involves blending the microencapsulated API with magnesium oxide and mannitol to aid in the release of the drug from the polymeric coating. These microparticles are further blended with other excipients and loosely compressed to maintain some degree of tablet porosity to aid dispersion. Compression forces need to be kept to a minimum so as not to disrupt the API taste-masking coating. The resultant tablet is relatively weak and friable and requires specific patented packaging technology (PakSolv, CIMA Labs) and use of aluminum blisters to protect the drug from moisture. Disintegration times are typically less than 40 s.

DuraSolv. The DuraSolv (CIMA Labs) technology is similar to OraSolv technology but uses increased compression forces during tableting such that the product is sufficiently robust to be packaged into traditional push-through blister packs or bottles. Durasolv technology incorporates the taste-masked active drug ingredients but may or may not contain the low-effervescence system. A consequence of increasing compression to improve robustness is a compromise in drug loading, which limits the product to fairly small doses. Both OraSolv and DuraSolv products are sensitive to moisture due to the presence of the effervescent system and must be packaged appropriately.


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