Title:
ARIPIPRAZOLE COMPOSITIONS AND METHODS FOR ITS TRANSDERMAL DELIVERY
Kind Code:
A1


Abstract:
The present invention discloses compositions of liquid and gel formulation containing aripiprazole in the form of a patch for transdermal delivery.



Inventors:
Plakogiannis, Fotios M. (Whitestone, NY, US)
Hossain, Anwar Muhammed (Congers, NY, US)
Application Number:
13/668500
Publication Date:
07/04/2013
Filing Date:
11/05/2012
Assignee:
PLAKOGIANNIS FOTIOS M.
HOSSAIN ANWAR MUHAMMED
Primary Class:
Other Classes:
514/253.07
International Classes:
A61K31/496
View Patent Images:



Foreign References:
WO2009060473A22009-05-14
Other References:
Lubrizol. TDS-730 "Viscosity of Carbopol Polymers in Aqueous Systems" Published 24 November 2009. (https://www.lubrizol.com/Life-Science/Documents/Pharmaceutical/Technical-Data-Sheets/TDS-730-Viscosity-Carbopol-in-Aqueous-Systems.pdf)
UNC. "The Pharmaceutics and Compounding Laboratory" (http://pharmlabs.unc.edu/labs/gels/agents.htm) accessed 5 August 2014
NMP. MSDS for N-methylpyrrolidone. (http://www3.imperial.ac.uk/pls/portallive/docs/1/7276131.PDF) May 2001.
Bhattacharjee, H.; Thoma, L. "Parenteral drug administration: routes of administration and devices" Pharmaceutical Dosage Forms: Parenteral Medications, Third Edition, Chapter 2, August 2010, pgs 7-29
Paudel, K.S. et al. "Challenges and opportunities in dermal/transdermal delivery" Ther. Deliv. July 2010, 1 (1), 109-131.
Baranda, L. et al. "Correlation between pH and irritant effect of cleansers marketed for dry skin" Int. J. Derm. 2002, 41, 494-499
Pathan, I.B.; Setty, C.M. "Chemical Penetration Enhancers for Transdermal Drug Delivery Systems" Trop. J. Pharm. Res. 2009, 8 (2), 173-179.
Paudel, K.S. et al. "Challenges and opportunities in dermal/transdermal delivery" Ther. Deliv. July 2010, 1 (1), 109-131
Pathan, I.B.; Setty, C.M. "Chemical Penetration Enhancers for Transdermal Drug Delivery Systems" Trop. J. Pharm. Res. 2009, 8 (2), 173-179
Trommer, H. et al. "Overcoming the Stratum Corneum: The Modulation of Skin Penetration" Skin Pharmacol Physiol 2006;19:106–121
Trommer, H. et al. "Overcoming the Stratum Corneum: The Modulation of Skin Penetration" Skin Pharmacol Physiol 2006;19:106–121
Primary Examiner:
ROSENTHAL, ANDREW S
Attorney, Agent or Firm:
CAESAR RIVISE, PC (Philadelphia, PA, US)
Claims:
What is claimed is:

1. A pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in gel form, comprising: aripiprazole in the amount of about 1 to 20% w/v; a gelling agent in the range of about 0.1% to 5% w/v; an enhancer selected from the group consisting of dimethylacetamide, dimethylformamide, decymethylsulfoxide, terpene and terpenoids, liposomes, niosomes, transferomes, ethanosomes, urea, lauric acid, myristc acid, and combinations thereof; wherein the pH of the composition is maintained at approximately 6 to 7.

2. The pharmaceutical composition of claim 1 wherein the gelling agent is poloxamer.

3. The pharmaceutical composition of claim 1 wherein the form is a patch for transdermal delivery.

4. The pharmaceutical composition of claim 1 wherein the dosage form is an ointment, cream, emulsion, or liposome.

5. The pharmaceutical composition of claim 1 further comprising about 40% N-methyl-2-pyrrolidone, about 40% dimethylsulfoxide, about 15% alcohol, and about 5% water.

6. The pharmaceutical composition of claim 5, further comprising ingredients selected form the group consisting of isopropyl alcohol, isopropyl myristate, PEG, and combinations thereof.

7. A pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in liquid form, comprising: aripiprazole present in the amount of 1 to 20% w/v; an agent selected from the group consisting of an alcohol, glycol, mineral oil, vegetable oil, and combinations thereof, an enhancer selected from the group consisting of dimethylacetamide, dimethylformamide, decymethylsulfoxide, terpene and terpenoids, liposomes, niosomes, transferomes, ethanosomes, urea, lauric acid, myristc acid, and combinations thereof; wherein the pH of the composition is maintained at approximately 6 to 7.

8. The pharmaceutical composition of claim 7 wherein the form is a patch for transdermal delivery.

9. The pharmaceutical composition of claim 7 being in the dosage form of an ointment, cream, emulsion, or liposome.

10. The pharmaceutical composition of claim 7 further comprising about 40% N-methyl-2-pyrrolidone, about 40% dimethylsulfoxide, about 15% alcohol, and about 5% water.

11. The pharmaceutical composition of claim 10, further comprising ingredients selected form the group consisting of isopropyl alcohol, isopropyl myristate, PEG, and combinations thereof.

12. A pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in gel form, comprising: aripiprazole in the amount of about 1 to 20% w/v; a gelling agent in the range of about 0.1% to 5% w/v; an enhancer selected from the group consisting of dimethylacetamide, dimethylformamide, decymethylsulfoxide, terpene and terpenoids, liposomes, niosomes, transferomes, ethanosomes, urea, lauric acid, myristc acid, and combinations thereof; about 40% N-methyl-2-pyrrolidone, 40% dimethylsulfoxide, 15% alcohol and 5% water; wherein the pH of the composition is maintained at approximately 6 to 7.

13. The pharmaceutical composition of claim 12, further comprising ingredients selected form the group consisting of isopropyl alcohol, isopropyl myristate, PEG, and combinations thereof.

14. A pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in liquid form, comprising: aripiprazole present in the amount of 1 to 20% w/v; an agent selected from the group consisting of an alcohol, glycol, mineral oil, vegetable oil, and combinations thereof, an enhancer selected from the group consisting of dimethylacetamide, dimethylformamide, decymethylsulfoxide, terpene and terpenoids, liposomes, niosomes, transferomes, ethanosomes, urea, lauric acid, myristc acid, and combinations thereof; about 40% N-methyl-2-pyrrolidone, about 40% dimethylsulfoxide, about 15% alcohol and about 5% water; wherein the pH of the composition is maintained at approximately 6 to 7.

15. The pharmaceutical composition of claim 14, further comprising ingredients selected form the group consisting of isopropyl alcohol, isopropyl myristate, PEG, and combinations thereof.

16. A pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in gel form, comprising about 2% ARPZ; about 25% DMSO; about 10% NMP; about 5% isopropyl alcohol (IPA); about 40% Ethyl Alcohol; about 15% PEG 400; about 0.5% carbomer; water q.s. to 100%.

17. The pharmaceutical composition of claim 16, wherein the pH of the composition is maintained at approximately 6 to 7.

18. A pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in liquid form, comprising about 2% ARPZ; about 25% DMSO; about 10% NMP; about 5% isopropyl alcohol (IPA); about 40% Ethyl Alcohol; about 15% PEG 400; about 0.5% carbomer; water q.s. to 100%.

19. The pharmaceutical composition of claim 18, wherein the pH of the composition is maintained at approximately 6 to 7.

Description:

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation in part of PCT/US2011/057080 filed Oct. 20, 2011, which claims benefit of U.S. Provisional Patent Application Ser. No. 61/407,591 filed Oct. 28, 2010.

BACKGROUND OF THE INVENTION

1. Field of Invention

The present invention relates to the field of transdermal delivery of pharmaceutical compositions, which have an acceptable in vitro performance and good bioavailability. In particular, the transdermal pharmaceutical compositions of the present invention include liquids or gels of aripiprazole in a patch dosage form.

2. Background of Invention

Aripiprazole (ARPZ) is the first of a new class of atypical antipsychotics (third generation). Biochemically, ARPZ is a partial agonist of the D2 family of dopamine receptors.1,2 It is active against positive and negative symptoms of schizophrenia.3,4 ARPZ is a quinolinone derivative, white crystalline powder, practically insoluble in water, with a low melting point (135-140° C.), MW 448.38 g/mole and partition coefficient of 4.54.

All references cited herein are incorporated herein by reference in their entireties.

BRIEF SUMMARY OF THE INVENTION

The invention provides a pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in gel form, comprising: aripiprazole in the amount of about 1 to 20% w/v; a gelling agent in the range of about 0.1% to 5% w/v; an enhancer selected from the group consisting of dimethylacetamide, dimethylformamide, decymethylsulfoxide, terpene and terpenoids, liposomes, niosomes, transferomes, ethanosomes, urea, lauric acid, myristc acid, and combinations thereof; wherein the pH of the composition is maintained at approximately 6 to 7. The invention further provides a composition of the invention wherein the gelling agent is poloxamer. The invention further provides a composition of the invention wherein the form is a patch for transdermal delivery. The invention further provides a composition of the invention wherein the dosage form is an ointment, cream, emulsion, or liposome. The invention further provides a composition of the invention further comprising about 40% N-methyl-2-pyrrolidone, about 40% dimethylsulfoxide, about 15% alcohol, and about 5% water. The invention further provides a composition of the invention further comprising ingredients selected form the group consisting of isopropyl alcohol, isopropyl myristate, PEG, and combinations thereof.

The invention provides a pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in liquid form, comprising: aripiprazole present in the amount of 1 to 20% w/v; an agent selected from the group consisting of an alcohol, glycol, mineral oil, vegetable oil, and combinations thereof, an enhancer selected from the group consisting of dimethylacetamide, dimethylformamide, decymethylsulfoxide, terpene and terpenoids, liposomes, niosomes, transferomes, ethanosomes, urea, lauric acid, myristc acid, and combinations thereof; wherein the pH of the composition is maintained at approximately 6 to 7. The invention further provides a composition of the invention wherein the form is a patch for transdermal delivery. The invention further provides a composition of the invention being in the dosage form of an ointment, cream, emulsion, or liposome. The invention further provides a composition of the invention further comprising about 40% N-methyl-2-pyrrolidone, about 40% dimethylsulfoxide, about 15% alcohol, and about 5% water. The invention further provides a composition of the invention further comprising ingredients selected form the group consisting of isopropyl alcohol, isopropyl myristate, PEG, and combinations thereof.

The invention provides a pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in gel form, comprising: aripiprazole in the amount of about 1 to 20% w/v; a gelling agent in the range of about 0.1% to 5% w/v; an enhancer selected from the group consisting of dimethylacetamide, dimethylformamide, decymethylsulfoxide, terpene and terpenoids, liposomes, niosomes, transferomes, ethanosomes, urea, lauric acid, myristc acid, and combinations thereof; about 40% N-methyl-2-pyrrolidone, 40% dimethylsulfoxide, 15% alcohol and 5% water; wherein the pH of the composition is maintained at approximately 6 to 7. The invention further provides a composition of the invention further comprising ingredients selected form the group consisting of isopropyl alcohol, isopropyl myristate, PEG, and combinations thereof.

The invention provides a pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in liquid form, comprising: aripiprazole present in the amount of 1 to 20% w/v; an agent selected from the group consisting of an alcohol, glycol, mineral oil, vegetable oil, and combinations thereof, an enhancer selected from the group consisting of dimethylacetamide, dimethylformamide, decymethylsulfoxide, terpene and terpenoids, liposomes, niosomes, transferomes, ethanosomes, urea, lauric acid, myristc acid, and combinations thereof; about 40% N-methyl-2-pyrrolidone, about 40% dimethylsulfoxide, about 15% alcohol and about 5% water; wherein the pH of the composition is maintained at approximately 6 to 7. The invention further provides a composition of the invention further comprising ingredients selected form the group consisting of isopropyl alcohol, isopropyl myristate, PEG, and combinations thereof.

The invention provides a pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in gel form, comprising about 2% ARPZ; about 25% DMSO; about 10% NMP; about 5% isopropyl alcohol (IPA); about 40% Ethyl Alcohol; about 15% PEG 400; about 0.5% carbomer; water q.s. to 100%. The invention further provides a composition of the invention wherein the pH of the composition is maintained at approximately 6 to 7.

The invention provides a pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery, wherein the aripiprazole is in liquid form, comprising about 2% ARPZ; about 25% DMSO; about 10% NMP; about 5% isopropyl alcohol (IPA); about 40% Ethyl Alcohol; about 15% PEG 400; about 0.5% carbomer; water q.s. to 100%. The invention further provides a composition of the invention wherein the pH of the composition is maintained at approximately 6 to 7. The invention provides that the pH of the composition is maintained at approximately 6 to 7 using HC1. The invention provides that the pH of the composition is maintained at approximately 6 to 7 using at least one buffer.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

The invention will be described in conjunction with the following wherein:

FIG. 1 is a graph showing Effect of Drug Concentration on the Flux of ARPZ through Cellulose Membrane from 0.5% CARBOPOL® 971 Gel Systems.

FIG. 2 is a graph showing Cumulative Amount of 5% ARPZ Permeated through Cadaver Skin from 0.5% CARBOPOL® Gel System

FIG. 3 is a graph showing Cumulative Amount of Drug Permeated through Human Cadaver Skin from 5% ARPZ in 0.5% CARBOPOL® Gel Systems with Enhancers (Fatty Acids)

DETAILED DESCRIPTION OF THE INVENTION

The invention provides a pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery. The invention provides a pharmaceutical composition of the invention wherein the aripiprazole is in a gel or liquid form. The invention provides a pharmaceutical composition of the invention wherein the aripiprazole is present in the amount of 1 to 20% w/v. The invention provides a pharmaceutical composition of the invention wherein the aripiprazole is present in the amount of 1 to 20% w/v. The invention provides a pharmaceutical composition of the invention wherein the gel contains a gelling agent in the range of about 0.1% to 5% w/v. The invention provides a pharmaceutical composition of the invention further comprising approximately 40% N-methyl-2-pyrrolidone, 40% Dimethylsulfoxide, 15% alcohol and 5% water.

The invention provides a pharmaceutical composition for transdermal delivery which comprises ARPZ 2%; DMSO at a concentration of about 10 to 40%, and at a preferred concentration of about 25%; NMP at a concentration of about 5 to 40%, and a preferred concentration is about 10%; Isopropyl alcohol (IPA) at a concentration of about 1 to 15%, and a preferred concentration is about 5%; Ethyl Alcohol at a concentration of about 15 to 40%, and a preferred concentration is about 40%; PEG 400 at a concentration of about 1 to 15%, and a preferred concentration is about 15%; CARBOPOL® 971P at a concentration of about 0.25 to 5%, and a preferred concentration is about 0.5%; and water, q.s. to 100%.

The invention provides a pharmaceutical composition of the invention being in the form of a liquid and comprising an alcohol, glycol, mineral oil, and/or vegetable oil. The invention provides a pharmaceutical composition of the invention wherein the composition is in a gel form and further comprises a gelling agent selected from the group consisting of natural polymers, semisynthetic polymers, synthetic polymers, carboxyvinyl polymers or carbomers, CARBOPOL® 940, CARBOPOL® 934, CARBOPOL® 971, poloxamer, polyacrylamide, polyvinyl alcohol, polyethylene and co-polymers thereof. The invention provides a pharmaceutical composition of the invention wherein the form is a patch for transdermal delivery. The invention provides a pharmaceutical composition of the invention being in the dosage form of an ointment, cream, emulsion, or liposome. The invention provides a pharmaceutical composition of the invention wherein the aripiprazole is present in the amount of 1 to 20% w/v.

The invention provides a pharmaceutical composition of the invention further comprising an enhancer. The invention provides a pharmaceutical composition of the invention wherein the enhancer is selected from the group consisting of lauric acid, myristc acid, water, sulfoxides, dimethylsulfoxide, dimethylacetamide, dimethylformamide, decymethylsulfoxide, pyrrolidones, fatty acid esters, fatty acids, alcohols, fatty alcohols and glycols, urea, essential oils, terpene and terpenoids, liposomes, niosomes, transferomes and ethanosomes.

The invention provides a pharmaceutical composition of the invention wherein the pH of the composition is maintained at approximately 6 to 7. The invention provides a pharmaceutical composition of the invention wherein the pH of the composition is maintained at approximately 6 to 7.

The invention will be illustrated in more detail with reference to the following Examples, but it should be understood that the present invention is not deemed to be limited thereto.

EXAMPLES

Example 1

ARPZ is practically insoluble in water and has been formulated as a liquid and gel dosage form (Table 1). All reported values are in weight/volume percentage (W/V)

TABLE 1
Composition of liquid and gel formulation of Aripiprazole (5% W/V)
W/VW/V
N-methyl-2-pyrolidone (NMP)40%40%
Dimethyl Sulfoxide (DMSO)40%40%
Ethyl Alcohol15%15%
Carbopol 971P0.5% 
Water 5%4.5% 
Total100.00%   100.00%   

An optimal mixture design of experiments was used to select the levels of the formulation variables. The optimum composition of a 1% W/V to 20% W/V ARPZ liquid formulation was predicted to have NMP 40%, DMSO 40%, Alcohol 15% and water 5% (Table 1). The gel formulation should contain a gelling agent in the range of about 0.1% to 5% W/V and the optimum APRZ composition should range from about 1% W/V to 20% W/V with about 0.5% W/V of the gelling agent. Therefore, the gel formulation was predicted to have a NMP of 40%, DMSO 40%, Alcohol 15%, CARBOPOL® 971 0.5%, and Water 4.5% (Table 1). However, Table 2 lists other combinations that also could produce successful liquid and gel ARPZ formulations in accordance with the present invention.

TABLE 2
Concentration Ranges of N-Methyl-2-Pyrolidone (NMP),
Dimethl Sulfoxide (DMSO), Ethyl Alcohol, and Water in
Liquid Aripiprazole Formulation
FormulationNMPDMSOAlcoholWater
1.5050
2.404020
3.404020
4.4040155
5.40401010
6.4040515
7.30302020
8.30303010
9.3040255
10.4030255
11.4545100
12.4540105

Other than these components, other solvents known to those skilled in the art suitable for use in the present invention can be used to prepare the liquid formulation, and combinations thereof, including but not limited to alcohols such as but not limited to (methyl, ethyl, butyl, propyl, isopropyl, isopropyl myristate, etc.), glycols such as, but not limited to (propylene, polyethylene, glycerin, etc.) mineral oils, vegetable oils, and others.

Example 2

The effect of gelling agents and their concentration on the permeation of ARPZ through artificial membranes and human cadaver skin was evaluated and two characteristic graphs are shown in FIGS. 1 & 2. The optimal desired composition of ARPZ gel formulation contains 0.5% W/V CARBOPOL® 971. ARPZ can be gelled by gelling agents, including but not limited to, natural polymers (such as agar, alginic acid and derivatives, cassia tora, collagen, gelatin, gellum gum, guar gum, pectin, potassium, or sodium carageenan, tragacanth, xanthan, etc.), semisynthetic polymers (such as methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, etc.) synthetic polymers (such as carboxyvinyl polymers or carbomers: CARBOPOL® 940, CARBOPOL® 934, CARBOPOL® 971, poloxamer, polyacrylamide, polyvinyl alcohol, polyethylene, and its co-polymers etc), and clays (such as silicates, etc). In addition, other than cellulose membranes, ARPZ can be evaluated with other artificial membranes including but not limited to silicone membranes (polydimethylsiloxane), liposome-coated membranes, solid-supported liquid membranes, lecithin organogel membranes and other. Besides the gel formulations of ARPZ, other dosage forms including, but not limited to, ointments, creams, emulsions, liposomes, etc. may be used.

Example 3

The effect of enhancers on the flux of ARPZ through human cadaver skin was evaluated and is shown in FIG. 3. The desired optimum composition of ARPZ gel formulation contained Lauric and Myristc acid. Apart from Lauric and Myristc acid enhancer, the ARPZ transdermal delivery can be influenced by enhancers including but not limited to water, sulfoxides, and similar chemicals, dimethylsulfoxide (DMSO), dimethylacetamide (DMAC), dimethylformamide (DMF), decymethylsulfoxide (DCMS) etc, pyrrolidones N-methyl-2-pyrrolidone (NMP), 2-pyrrolidon (2p), etc., fatty acids esters (butyl ethanoate, ethyl ethanoate, ethyl oleate, isopropyl myristate, isopropyl palmiate, methyl ethanoate etc), fatty acids (capric, caprylic, lauric, oleic, myristic, linoleic, stearic, palmitic etc), alcohols, fatty alcohols and glycols (nathanol, dodecanol, propylene glycols, glycerol etc), urea, essential oils, terpene and terpenoids (limonene, thymol, cineole etc), liposomes, niosomes, transferomes, ethanosomes etc.

Example 4

The effects of pH on the permeation of ARPZ through human cadaver skin were evaluated and a characteristic graph is shown in FIG. 2. The preferred optimum composition of ARPZ gel transdermal formulation had a pH in the range of approximately 6 to 7. Other than these optimal pH values, the ARPZ transdermal delivery may be influenced by pH values outside of the preferred range, but to a lesser extent. Thus, the present invention may still be achieved outside of the preferred pH range of approximately 6 to 7, depending upon the circumstances of use.

The systems of this discovery can deliver ARPZ at a flux between 50 mcg/ch-2. h and 800 mcg/ch-2.h, which can produce the required therapeutic ARPZ blood levels. Flux rate can be changed by modifying such parameters as ARPZ initial concentration, surface area of the patch, pH of the formulation, vehicle composition, enhancer type and composition, etc., in accordance with the teachings of the present invention.

Optimum therapeutic outcome requires not only a proper drug selection but also an effective drug delivery. Psychotropic drug compliance of rigorous regular medication schedules is of great importance. In many instances, oral administration of psychotropic agents is considered a less than optimal delivery system due to patient non-compliance5. Transdermal delivery of psychotropic drugs, especially with prolonged duration of action, would be valuable in increasing medication compliance, especially in the geriatric population. Further, potential advantages of ARPZ transdermal delivery are as follows: lack of hepatic first pass effect; eliminating the potential for over- or under-dosing; allowing the flexibility of terminating the drug administration by simply removing the patch; providing a simplified therapeutic regimen, thereby assisting medication compliance in the geriatric population.

Example 5

A transdermal composition of Aripiprazole is shown below:

ARPZ 2%
DMSO25%
NMP10%
Isopropylalcohol (IPA) 5%
Ethyl Alcohol40%
PEG 40015%
Carbopol 971P0.5% 
HClq.s. to pH 6-7
WATERq.s. to 100%

While the invention has been described in detail and with reference to specific examples thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.

REFERENCES

  • 1. Inoue, T., Domae, M., Yamada, K., and Furukawa, T. Effects of the novel antipsychotic agent 7-([4-2,3-dichlorophenylo-1-piperazinyl]b Neuroutyloxyo-3,4-dihydro2 (1H)-quinolinone (OPC-14597) on prolactin release from the rat anterior pituitary. J. Pharmacol. Exp. Ther. 1996; 277(1):137-143.
  • 2. Burris, K. D., Moiski, T. F., Ryan, E., Xu, C., Tottori, K., Kikuchi, T., Yocca, F. D, and Molinoff, P. B. Aripiprazole is a high affinity partial agonist at human D2 dopamine receptors. Int. J. Neuropsychopharmacol. 2000; 3(Suppl. 1), S129.
  • 3. Petrie, J. L., Saha, A. R., and McEvoy, J. P. Aripiprazole, a new atypical antipsychotic: Phase II clinical trial results. Eur. Neuropsychopharm 1997; 7 (Suppl 2): 5227.
  • 4. Saha, A. R., McQuade, R., Carson, W. H., Ali, M., W., Durbar, G. C., and Ingenito, G. Efficacy and safety of Aripiprazole and Risperidone vs. Placebo in patients with schizophrenia and schizoaffective disorder. World J. Biol Psych 2001; 2 (Suppl 1): 305S.
  • 5. Geeta, A., Sanju, D., Psychotropic Drugs and Transdermal Delivery. An Overview. Int. J. of Pharma and Bio Science, 2001; V 1(2).