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Effect of formulation on methylphenidate release patterns

Clinical implications

  • Review Article
  • Published:
American Journal of Drug Delivery

Abstract

Attention-deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children. Currently, the most widely prescribed therapy for ADHD is methylphenidate. Several formulations of methylphenidate have been developed that modify the delivery of the drug into the body. These include immediate-release (IR) tablets and modified-release preparations including sustained-release tablets, controlled-delivery capsules and tablets, and transdermal delivery systems. The IR tablet is taken two or three times daily and has been demonstrated to show efficacy through its rapid onset of action. The modified-release formulations deliver methylphenidate at a controlled rate and are administered once daily; they were developed to mimic the efficacy of the IR tablet by controlling drug release. The latest formulation development efforts have been directed towards combining the rapid release and onset of action of an IR component with an extended-release component that would maintain drug levels and allow for once-daily administration.

The rationale for the development of various delivery systems of methylphenidate stems from the need for drug coverage for at least 8 hours for ADHD patients. This would maintain efficacy over the entire school day and would eliminate the need for repeated administrations while the patient was at school. Early formulation development targeted a constant-release profile or an apparent zero-order input with the intention of maintaining plasma drug levels at a constant level for the required time period. However, it was demonstrated that the constant delivery of methylphenidate did not provide equivalent efficacy to the repeated administration of the IR product over the school day and resulted in tolerance to the effects of the drug. This suggested that sustained-release formulations that maintained constant drug levels over the treatment period would not result in the optimal therapeutic condition. In contrast, a drug delivery profile that maintained a drug release pattern with increase-release kinetics would be able to overcome the tolerance that was observed with the constant delivery formulations. Therefore, the formulation development for modified-release once-daily administration products of methylphenidate has been targeted to mimic the repeated administrations of IR methylphenidate.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgment

The authors would like to thank John Pentikis and Linda Gonzalez for their assistance in the preparation of this manuscript.

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.

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  1. A Division of ICON plc, GloboMax®, 7250 Parkway Drive, Suite 430, Hanover, Maryland, MD 21076, USA

    Helen S. Pentikis

  2. P’Kinetics International Inc., Pembroke Pines, Florida, USA

    Mario A. González

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  1. Helen S. Pentikis
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  2. Mario A. González
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Correspondence to Helen S. Pentikis.

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Pentikis, H.S., González, M.A. Effect of formulation on methylphenidate release patterns. Am J Drug Deliv 3, 47–54 (2005). https://doi.org/10.2165/00137696-200503010-00005

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