College of Psychiatric and Neurologic Pharmacists

Dosage formulation technologies are undergoing a renaissance, spanning nanotechnology, polymer chemistry, aerosolization, and smart skin patches. The development of new dosage formulations of antipsychotic medications, focuses upon modified oral release, ultra-fast acting inhalation, and long-acting injectable therapies.  

Long-acting injectable therapies are described spanning the gamut from oil based esterified drug (fluphenazine, haloperidol, zuclopenthixol) formulations through microcrystalline and nanotechnology suspensions for injection (olanzapine, paliperidone, aripiprazole) and to polymeric encapsulation, i.e., microspheres used for risperidone. This array of formulation technologies provide PK driven modifications in pharmacodynamic effects that are intended to provide greater efficacy and reduced adverse effects. Long-acting products can undergo spurts of release that are probably not clinically significant, since the variation is less than usual oral fluctuations. However, occasionally dose-dumping results in dystonia (fluphenazine decanaote) or rarely in excessive sedation/impaired consciousness (olanzapine pamoate), illustrating the need for these formulations to be rigorously evaluated and stored/handled properly. Haloperidol decanoate demonstrates PK/PD improvements such as equivalent efficacy with lower extrapyramidal rates than oral therapy. Oral extended release formulations appear to offer some advantages including higher starting doses with less need for titration to therapeutic targets (quetiapine ER), and/or potentially greater potency than anticipated due to reduced intra-subject within dose variation (paliperidone OROS). Aerosolized small particle technology might allow inhalation of antipsychotics (e.g. loxapine) or sedatives, providing another alternative in treating acutely ill patients. Modified dosage formulations of antipsychotics appear to have the potential to result in drug concentrations remaining, for more time per day, within the therapeutic target range for D2 receptor occupancy. The pharmacokinetic-pharmacodynamic interface is explored via use of simulations and a mechanism of action driven hypotheses. Less extrapyramidal symptoms with equivalent clinical efficacy in the short term, and possibly greater effect (or lower exposures for maintenance of effect) are consistent with these models and the data. However, there is a paucity of outcomes studies to validate these intuitive assumptions. It is also assumed that long-acting antipsychotics or once daily dosing (from multiple daily dosing), should improve adherence and, hence, outcomes. 

Existing drugs have also had new formulations developed: oral dissolving tablets (e.g., arpipiprazole, clozapine, olanzapine, risperidone). Many demonstrate no significant differences from conventional oral therapy. The pharmacokinetics of controlled/extended release oral dosage forms employ a variety of mechanisms (e.g., enteric coatings, layered release systems, osmotic release mechanisms) but all attempt to reduce acute adverse effects, complexity of the dosage regimen, or improve the bioavailability. Additionally, non-parenteral novel dosage forms could include transdermal delivery systems that allow smoother concentrations and extended duration of action compared to oral therapies, can bypass problematic metabolic interactions, or be part of nano-medical devices that diagnose, measure a laboratory parameter, and dose the patient.

1. Identify five strategies to modify delivery of medications.
2. Explain what are the possible Pharmacodynamic advantages, which result from dosage formulation related changes in drug concentrations at their site of actions.
3. Identify future strategies for drug delivery and monitoring systems.
4. Summarize data available supporting (or not) the advantages of novel dosage forms.
5. Describe research strategies (and clinical approaches) to study the safety and efficacy of novel antipsychotic dosage forms.

Activity Dates: 04/22/2009 - 04/22/2012
ACPE Contact Hours: 1.0
ACPE Number: 0284-0000-09-014-H01-P
Nursing Credit Reminder: Note that ACPE and ACCME credit is accepted for certification renewal.

This course is provided online at cpnp.org and consists of the speaker audio and slides. A PDF file of the slides is also provided and access is available to participants indefinitely although ACPE credit is available only through the course expiration date.

Participants in this course must complete an examination and achieve a score of 60% or greater. Successful completion of the course also requires the completion of a course evaluation. ACPE statements of credit can be retrieved by participants online at cpnp.org immediately upon successful completion of the course.

If you are a pharmacist, nurse practitioner or other healthcare professional involved in the medication therapy management of psychiatric and/or neurological patients, we invite you to participate in this online course.

This programming was supported in part by grants from Bristol-Myers Squibb, Forest Laboratories, Inc., Lilly, Schering-Plough, Cyberonics, and Shire.