FORM 2
THE PATENTS ACT 1970 (Act 39 of 1970)
(SECTION 10)
"ORALLY DISINTEGRATING TABLETS OF OLANZAPINE"
Glenmark Pharmaceuticals Limited, an Indian Company,
registered under the Indian company's Act 1957 and
having its registered office at
B/2, Mahalaxmi Chambers, 22, Bhulabhai Desai Road
Post Box No. 26511
Mumbai - 400 026, India
THE FOLLOWING SPECIFICATION DESCRIBES THE NATURE OF THE INVENTION
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OLANZAPINE ORALLY DISINTEGRATING TABLETS
BACKGROUND OF THE INVENTION
1. Technical Field
The present invention generally relates to a novel pharmaceutical composition of Olanzapine orally disintegrating tablet using direct compression technique and process for making the same.
2. Description of the Related Art
Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepme class. The chemical designation is 2-methyl-4-(4-methyl-l-piperazinyl)-10//-thieno[2,3-6] [l,5]benzodiazepine, and having structure :

Olanzapine is a novel antipsychotic agent marketed by Lilly & Co. It has a pleotrophic pharmacology and affects dopaminergic, serotonergic, muscarinic and adrenergic activities. Clinical studies and trials suggest olanzapine is superior to haloperidol and also maybe superior to risperidone in terms of efficacy and side-effect profiles.
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Olanzapine belongs to a large category of medications that affect the mind, called psychotropics. Antipsychotic medicines are psychotropic medications that treat the symptoms of psychotic disorders such as schizophrenia. Olanzapine is a newer kind of antipsychotic medication known as an atypical antipsychotic.
Olanzapine is believed to work by balancing the chemicals naturally found in the brain. Olanzapine may help relieve your symptoms so you feel better. As your symptoms improve, you will be better able to start getting your life back on track.
Antipsychotic medicines are used to treat the unique symptoms of psychosis, such as hallucinations and delusions. They work to help you concentrate better, think more clearly, and improve bothersome symptoms, such as fears and voices. They may be especially valuable after a relapse or a flare-up of symptoms. Antipsychotic medicines may work in three ways: They may adjust the imbalance of chemicals in your brain.They may help you handle stress more successfully. They may make it easier for you to cope with your symptoms.
US6024981 by Cima Labs Inc. invention is directed to a hard tablet that can be stored, packaged and processed in bulk. Yet the tablet dissolves rapidly in the mouth of the patient with a minimum of grit. The tablet is created from an active ingredient mixed into a matrix of a non-direct compression filler and a relatively high lubricant content. The invention disclosed herein in this specification achieved the manufacture of tablet solid oral dosage form using directly compressible ingredients and relatively low content of lubricants for Olanzapine.
U.S. Pat. No. 5,178,878. Zydis, on the other hand, produces a rapidly dissolvable, freeze-dried, sugar matrix to produce a rapidly dissolving tablet. While these dosage forms are effective, they provide significant problems in terms of production, storage, transport and during consumer usage. They are also significantly more costly to produce.
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US5464632 patent assigned to Laboratoires Prographarm discloses a rapidly disintegratable multiparticulate tablet the excipient mixture of which is suitable for imparting a disintegration rate such that the tablet disintegrates in the mouth in an extremely short time, notably in less than sixty seconds, characterized by the fact that the active substance is present in the form of coated microcrystals or coated or uncoated microgranules.The present invention covered and disclosed herein in this specification is not using any technique of preparation of microgranules but disclosed process is simple technique of direct compression using directly compressible ingredients.
So there remains a need for developing an orally disintegrating tablets of moisture sensitive drug like olanzapine in a stable dosage form. This patent specification discloses the invention for Olanzapine orally disintegrating tablet and method for making the same using directly compressible technique as we found this technique is reported nowhere in the prior arts.
SUMMARY OF THE INVENTION
In accordance with one embodiment of the present invention is to make a novel , stable composition of Olanzapine using direct compression technique.
In accordance with a second embodiment a process for preparing a stable pharmaceutical
formulation is provided, the process comprising 1) Sift Olanzapine, Mannitol,
Microcrystalline cellulose, Aspartame and Crosslinked PVP through #40 sieves and Magnesium stearate through #60 sieve.2) Mix Olanzapine , Mannitol, Microcrystalline cellulose, Aspartame and Croslinked PVP by geometric mixing using conta blender.3) Lubricate the blend of step 2 with Magnesium stearate using conta blender.4) Compress the lubricated blend of step 3 in to tablets using rotary compression machine.
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In accordance with a third embodiment of the present invention, the oral dosage form is prepared in a manner that it disintegrates in the mouth cavity and releases drug within 60 seconds.
In accordance with the fourth embodiment of the present invention is to provide the compliance to the patients who can not swallow the tablet dosage form.
In further accordance of this invention is the tablets are prepared using directly compressible ingredients.
Yet another aspect of the invention is excipients selected to prepare Olanzapine tablet selected from the category of directly compressible ingredients e.g. directly compressible mannitol, directly compressible lactose, directly compressible microcrystalline cellulose etc.
Further aspect of the invention includes optionally sweeteners and are used in this composition are selected from the group e.g. sodium saccharine, aspartame, Glycyrrhizin powder etc. Most preferred sweetener is Aspartame.
Flavors and preservatives can be used in this invention optionally.
DEFINITIONS
The term "treating" or "treatment" of a state, disorder or condition as used herein means: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a mammal that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition, i.e., arresting or reducing the development of the disease or at least one clinical or
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subclinical symptom thereof, or (3) relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms. The benefit to a subject to be treated is either statistically significant or at least perceptible to the patient or to the physician.
The term "therapeutically effective amount" as used herein means the amount of a compound that, when administered to a mammal for treating a state, disorder or condition, is sufficient to effect such treatment. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the mammal to be treated.
By "pharmaceutically acceptable" is meant those salts and esters which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use. The term "subject" or "a patient" or "a host" as used herein refers to mammalian animals, preferably human.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The disclosed invention in this specification is a formulation which is physicochemically stable solid oral composition of Olanzapine prepared by direct compression method.
The active principle of this invention is Olanzapine which is a moisture sensitive drug and get degradates in the presence of moisture.
Inert excipients selected for making olanzapine tablets are prepared in such a way that they are directly compressible in nature.
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Directly compressible ingredients are selected form the group e.g. directly compressible mannitol, directly compressible lactose, directly compressible microcrystalline cellulose etc.
Sweeteners are used in this composition are selected from the group e.g. sodium saccharine, aspartame, Glycyrrhizin powder etc. Most preferred sweetener is Aspartame.
Flavours and preservatives can be used in this invention optionally.
All the excipients in this category are found tobe having low moisture content.
EXAMPLE (1)
Product: Olanzapine Orodispersible Tablets 10 mg
Composition

Sr. no. Ingredients Mg/ tablet % WAV of Tablet
1. Olanzapine form I 10.00 11.11
2. Mannitol (Perlitol SD 200) 38.15 42.39
3. Microcrystalline cellulose (Avicel PH 101) 36.00 40.00
4. Aspartame 0.45 0.50
5. Croslinked PVP 4.50 5.00
6. Magnesium stearate 0.90 1.00
Manufacturing process:
1) Sift Olanzapine form I, Mannitol, Microcrystalline cellulose, Aspartame and Croslinked PVP through #40 sieves and Magnesium stearate through #60 sieve.
2) Mix Olanzapine form I, Mannitol, Microcrystalline cellulose, Aspartame and Croslinked PVP by geometric mixing using conta blender.
3) Lubricate the blend of step 2 with Magnesium stearate using conta blender.
4) Compress the lubricated blend of step 3 in to tablets using rotary compression machine.
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The above examples is provided to enable one skilled in the art to practice the invention and are merely illustrative of the invention. The examples should not be read as limiting the scope of the invention as defined in the features and advantages.
Dated this twenty fourth (24th) day of May 2006

Taranpreet Lamba. ( Sr. Manager-IPM)
Glenmark Pharmaceuticals Limited
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