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Extended Release formulations of Nevirapine

IP.com Disclosure Number: IPCOM000242918D
Publication Date: 2015-Aug-29
Document File: 2 page(s) / 47K

Publishing Venue

The IP.com Prior Art Database

Abstract

Nevirapine, a Non-nucleoside reverse transcriptase inhibitor has become mainstay of antiretroviral therapy. Extended release formulations are generally preferred for drug such as Nevirapine. However, the narrow therapeutic window coupled with poor physicochemical properties of Nevirapine make the development of an extended release formulation unusually challenging. The present disclosure provides various extended release formulation of Nevirapine. These formulations could be in the matrix type or a release controlling polymer could be coated on the IR part. Preferably, hydroxylpropyl methyl cellulose (HPMC K4M Premium CR) is used to make the formulation. Nevirapine used for making the solid oral preparation has particles size of D90 less than or equal to 15µm.

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Extended Release formulations of Nevirapine 

Non-nucleoside reverse transcriptase inhibitor (NNRTI) based antiretroviral therapy (ART) has become increasingly popular as the first regime of choice in HIV treatment. One of the most used NNRTI drug is Nevirapine (11-cyclopropyl-5, 11-dihydro-4-methyl-6H-dipyrido [3,2-b:2',3'-e][1,4] diazepin-6-one).

Structurally, Nevirapine is a member of the dipyridodiazepinone chemical class of compounds; it blocks polymerase activity after binding directly to the HIV-1 reverse transcriptase leading to disruption of the enzyme’s catalytic site. Antiretroviral therapy with Nevirapine has demonstrated significant activity in HIV infected patients in combination drug with highly active antiretroviral therapy. In humans, Nevirapine is well absorbed orally with an estimated absolute bioavailability of about 90%. 

Generally Nervirapine immediate release 200 mg tablets are taken twice a day. USFDA approved, “Viramune XR” tablet (Innovator: Boehringer Ingelheim), is an extended release formulation that is intended to be administered once daily in order to maintain a therapeutically appropriate blood level of the active ingredient, Nevirapine.

Extended formulations are generally designed to be gradually absorbed during transit through the intestines, where the pH is high. Nevirapine being a weak base exhibits low solubility in the intestines. Further, for a drug to be safe, tolerable and effective, the plasma level must never be allowed to fall below the threshold at which viral replication is inhibited and it must never rise to the level at which there is toxicity or intolerance. For Nevirapine, the band between the two is relatively narrow. The poor physicochemical properties of Nevirapine make the development of an extended release formulation unusually challenging.

Extended release oral pharmaceutical compositions of Nevirapine containing excipients as summarised in Table - 1 were prepared. The composition may be in the form of a powder, granule or pellets or a unit dosage form, for example such as a tablet or capsule. The pharmaceutical compositions were produced by standard processes, for instance by dry granulation, wet granulation, direct compression. The conventional blending, granulating, sugar-coating, dissolving or lyophilizing processes may be employed in the preparation of pharmaceutical dosage form.

Further, the dosage formulation comprises the active agent and excipients in the form of particles having a particle size distribution that allows for the ease of processing the material, for example into capsules or tablets, without segregation of the excipients. The desired particle rang...