GB2625579A - An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same - Google Patents
An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same Download PDFInfo
- Publication number
- GB2625579A GB2625579A GB2219356.9A GB202219356A GB2625579A GB 2625579 A GB2625579 A GB 2625579A GB 202219356 A GB202219356 A GB 202219356A GB 2625579 A GB2625579 A GB 2625579A
- Authority
- GB
- United Kingdom
- Prior art keywords
- orally disintegrating
- range
- disintegrating tablet
- tablet according
- gabapentin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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Abstract
An orally disintegrating tablet comprising 30-70% w/w gabapentin, a diluent, 0.5-10% disintegrant and 0.5-3% stabiliser. The diluent may be 15-50% microcrystalline cellulose (MCC). At least 30% of the MCC may have a particle size of 70-100 µm and a bulk density of 0.26-0.34 g/ml or at least 70% may have a particle size below 75 µm and a bulk density of 0.1-0.15 g/ml. The diluent may be 5-30% maize starch or 15-55% of an MCC and maize starch combination. The orodispersable tablet may comprise binders, sweeteners and lubricants. Preferably, the disintegrant is crospovidone, stabiliser is poloxamer 407, lubricant is 0.5-4.5% magnesium stearate, binder is 0.5-6% hydroxypropyl cellulose and sweetener is 0.05-2% acesulfame potassium. The tablet may comprise magnesium stearate, hydroxypropyl cellulose, acesulfame potassium and crospovidone. The diluent and disintegrant may be in a ratio between 10:1 and 15:1. The tablet may be for treatment or prevention of postherpetic neuralgia and peripheral neuropathic pain. The tablet may dissolve in under 3 minutes, be stable for at least 3 months and be produced by sieving and mixing gabapentin and maize starch, blending with sieved MCC, crospovidone, hydroxypropyl cellulose, poloxamer 407, acesulfame potassium and magnesium stearate, compressing into a tablet and packaging.
Description
An Orally disintegrating tablet conta' * g Gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same
Field of the Invention
The present invention relates to a pharmaceutical composition of Gabapentin. The present invention relates to an orally disintegrating tablet of Gabapentin or pharmaceutically acceptable salts thereof for oral administration. The present invention also relates to the process of the preparation of the same
Background of the Invention
Gabapentin was first disclosed in the US 4024175. Gabapentin is a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
The primary mode of action appears to be at the auxiliary a25-1 subunit of voltage- gated calcium channels The major function of these subunits is to facilitate the movement of pore-forming a28-1 subunits of calcium channels from the endoplasmic reticulum to the cell membrane of pre-synaptic neurons. Gabapentin appears to inhibit the action of a28-1 subunits, thus decreasing the density of pre-synaptic voltage-gated calcium channels and the subsequent release of excitatory neurotransmitters.
Gabapentin is indicated for the treatment of postherpetic neuralgia and various types of peripheral neuropathic pain, such as painful diabetic neuropathy in adults and partial-onset seizures in paediatrics The 1UPAC name of gabapentin is 2-[]-(amino methyl) cyclohexyllacetic acid. The plasma half-life of gabapentin in patients with normal renal function is 5-7 hours Gabapentin is a high-water solubility and low permeability drug which makes it belong to BCS Class-Ill in the Biopharmaceutical classification system.
Gabapentin is marketed, particularly as an oral tablet, capsule, or solution. The commercially marketed products of Gabapentin in tablet form are available in five dosage strengths: 100, 300, 400, 600, and 800 mg for oral administration. Orally disintegrating tablets provides a good mouth feel property that improves patient compliance, particularly for paediatric patients. Moreover, Gabapentin is a freely water-soluble drug, making it a suitable drug for orally disintegrating tablet.
The marketed tablet of gabapentin is available in large size which is difficult to swallow for elderly, paediatrics resulting in patient noncompliance Therefore, Gabapentin is a good candidate for formulating the orally dispersible tablet as it is easy to swallow and would provide patient compliance for paediatrics, geriatric and psychiatric patients disabled bedridden patients, and for traveling and busy people, who do not have ready access to water or difficulty in swallowing.
The orally disintegrating tablet of the present invention is a pharmaceutical formulation that rapidly disintegrates in the mouth which helps in easy administration of tablet and provide accurate dosing as compared to liquid formulations.
EP 1784174A1 discloses a stable pharmaceutical composition comprising gabapentin as the active ingredient, tribasic calcium phosphate as a sliding agent, hydrogenated castor oil as a lubricant, sorbitol and alginic acid in mixture as diluents. The manufacturing process of invention involves a mixture of powders of gabapentin and inactive ingredients are mixed properly in a mixer for 10 minutes at room temperature The final powder mixture thus obtained are filled into capsules EP2923694A1 discloses a liquid pharmaceutical solution comprising gabapentin or a pharmaceutically acceptable salt, solvate, or hydrate thereof and one or more pharmaceutically acceptable excipients. The manufacturing process of this invention is carried out under nitrogen gas as follows: A Tank filled with water, to this Maltitol solution, is added Thereafter, sodium benzoate and di sodium EDTA as an antioxidant are added to this solution and mixed to obtain a homogeneous mixture and then Gabapentin is added to this pre-mixed solution Mixing other excipients to the final solution to achieve complete dissolution of ingredients. The final mixture is filtrated and filled into bottles.
EP1558218A1 discloses the conventional tablet comprising gabapentin and one or more excipients. The manufacturing process of this invention involves a wet granulation method as per following steps: a first portion of a binder is added to dried mixture of gabapentin and one or more excipients as combination or in separate way. To the dried granules, a second portion of binder in solution or dispersion form is added, followed by drying granules and then compressing dried granules into tablets.
EP1513504A1 discloses the sustained-release tablet comprises gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate-controlling polymer. The manufacturing process of this invention involves forming granules by mixing gabapentin with rate-controlling polymer and inactive ingredients, a water or binder solution is added to pre-mixed granules followed by drying the wet granules and compressed into tablets which provides gabapentin release for up to 12 hours.
1JS20090176882A1 discloses the gastric retentive oral dosage form of gabapentin for once or twice daily dose administration for improving patient compliance The process of this invention involves dispersing gabapentin in hydrophilic polymer that upon ingestion into gastric fluid swells to a size sufficient to achieve retention of the dosage form in the stomach in a fed mode for a period of at least about five hours
Summary of the Invention
The present invention provides an orally disintegrating tablet that comprises Gabapentin or phannaceutically acceptable salts thereof, Gabapentin is a good candidate for formulating orally disintegrating tablet that can provide good palatability and taste-masking properties for improving patient compliance.
Another embodiment of the invention provides the orally disintegrating tablet containing Gabapentin or pharmaceutically acceptable salts thereof, the diluent, and at least one or more ingredient such as a binder, a disintegrant, a stabilizer, a lubricant and a sweetener.
Further, another embodiment of the present invention that involves a process for preparing the orally disintegrating tablet. The orally disintegrating tablet is 15 manufactured by the direct compression method.
Another embodiment of the present invention can effectively treat postherpetic neuralgia and various types of peripheral neuropathic pain, such as painful diabetic neuropathy in adults and partial-onset seizures in paediatrics.
Obiects of the Invention The principal object of the present invention is to provide an orally disintegrating tablet of Gabapentin or pharmaceutically acceptable salts thereof It is further another object of the present invention to provide fast disintegration and dissolution of the dosage form as it gets in contact with saliva.
Yet another object of the present invention is to provide taste-masking properties and present pleasant palatability for paediatrics and also for administration to patients who cannot swallow, like the elderly, stroke victims, and bedridden patients; who do not have ready access to water.
Detailed description of the Invention
The present invention is an orally disintegrating tablet suitable for oral administration comprising gabapentin or pharmaceutically acceptable salts thereof with fast disintegrating properties as compared to conventional solid dose forms.
As per one embodiment of the present invention, gabapentin or pharmaceutically acceptable salts thereof, is present in the range of about 30%w/w to about 70%w/w, preferably in the range of about 40%w/w to about 60%w/w.
The term "about", as and when used in this specification, means +10 % of the mentioned value.
As per one embodiment of the present invention, the composition comprises a diluent selected from the group consisting of spray-dried lactose, dicalcium phosphate, dextrates, microciystalline cellulose, dextrose, maize starch, fructose, Sorbitol, pregelatinized starch, starch, xylitol, sucrose, Sorbitol, maltodextrin, maltose, mannitol or combinations thereof In the present invention, combination of microcrystalline cellulose and maize starch is preferred as a diluent in the range of about 15%w/w to about 55%w/w, preferably in the range from about 30%w/w to about 45%w/w. Microcrystalline cellulose is present in the range of about 15%w/w to about 50%w/w, preferably in the range from about 20%w/w to about 40%w/w and maize starch is present in the range from about 5%w/w to about 30%w/w, preferably in the range from about 7.0%w/w-to about 25.0%w/w. Maize Starch is used as a diluent as starches are known to swell upon contact with water through a wicking mechanism. Microcrystalline cellulose has a fast-wicking rate of water and small elastic deformation. The combination of microcrystalline cellulose and maize starch as diluents can provide fast disintegrating properties to the tablets.
As per another embodiment of the present invention, 30% of total weight of microcrystalline cellulose, which is characterized in that the average particle size of the microcrystalline cellulose particle is the range from about 70 nm to about 100 nm, preferably from about 90 nm to about 100 nm and the bulk density is in the range from about 0.26g/m1 to about 0.34 g/ml, preferably in the range from about 0.30g/m1 to about 0.33g/m1 and remaining 70% of microcrystalline cellulose, which is characterized in that the particle size of the microcrystalline cellulose is lesser than 75 ttm preferably lesser than 70 p.m and the bulk density is in the range from about 0.10g/cm3 to about 0.15 g/cm3, preferably in the range from about 0.11g/cm3to about 0.14g/cm3.
As per one more embodiment of the present invention, the disintegrant selected from the group consisting of Modified starches, cross-linked polyvinylpyrrolidone, croscarmellose sodium, soy polysaccharide, Cross-linked alginic acid, gell an gum, calcium Silicate or combinations thereof Crospovidone is preferred as a disintegrant for the present invention in the range from about 0.5%w/w to about 10.0%w/w, preferably in the range from about 1.5%w/w to about 7.5%w/w. Crospovidone quickly wicks saliva into the tablet to generate the volume expansion and hydrostatic pressures necessary to provide rapid disintegration in the mouth.
As per one embodiment of the present invention, a stabilizing agent selected from the group consisting of Poloxamers, Amino acid-based stabilizers, sodium alginate, sodium carboxymethyl cellulose (CMC), guar gum, locust bean gum, carrageenan, gelatin, and pectin, Povidone, Polyvinyl alcohol, sodium lauryl sulfate or combinations thereof Poloxamer 407 is preferred as stabilizer for the present invention. Poloxamer 407 is present in the range from about 0.5%w/w to about 3.0%w/w, preferably in the range from about 1.0%w/w to about 2.0')/ow/w.
As per one another embodiment of the present invention, a lubricant selected from the group consisting of boric acid, magnesium stearate, sodium stearyl fumarate, micronized poly oxy ethylene glycol, leuc ne, sodium benzoate, sodium acetate, sodium lauryl sulfate, stearic acid, sodium stearate, sodium oleate, calcium stearate, waxes or combinations thereof Magnesium stearate is preferred as a lubricant for the present invention and is present in the range from about 0.5%w/w to about 4.5% w/w, preferably in the range from about I.0%w/w to about 2.5%w/w.
As per one more embodiment of the present invention, a sweetener selected from the group consisting of cyclamate, acesulfame potassium, neo hesperidin dihydrochalcone, monoammonium glycyrrhizinate, saccharin sodium, sucralose, saccharin, aspartame or combinations thereof Acesulfame potassium is preferred as a sweetener for the present invention. Acesulfame potassium is present in the range from about 0.05w/w to about 2%w/w, preferably in the range from about 0.30%w/w to about I.5%w/w.
As per one embodiment of the present invention, a suitable binder for the present invention can be selected from the group consisting of alginic acid, carbomer, ethyl cellulose, gelatin, glucose, guar gum, hydroxy ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, polydextrose, polyethylene oxide, and povidone K30 or combinations thereof Hydroxypropyl cellulose is preferred as a binder for the present invention. Hydroxypropyl cellulose is present in the range from about 0.5% w/w to about 6.0% w/w, preferably in the range from about 1 %w/w to about 3 %w/w.
As per one another embodiment of the present invention, the orally disintegrating tablet comprising Gabapentin or pharmaceutically acceptable salts thereof is present in the range from about 30%w/w to about 70%w/w, preferably in the range from about 40%w/w-to about 60%w/w, a disintegrant present in the range from about 0.5 %w/w to about 10% w/w preferably in the range from about 1.5 %w/w to about 7.5%w/w and a diluent is present in the range from about 15%w/w to about 55%w/w, preferably in the range from about 30%w/w to about 45%w/w. The orally disintegrating tablet further comprises at least one pharmaceutically acceptable excipient selected from sweeteners, binders, stabilizers, lubricants or combination thereof As per preferred embodiment of the present invention, the orally disintegrating tablet comprising Gabapentin or pharmaceutically acceptable salts thereof is present in the range from about 30%w/w to about 70%w/w, preferably in the range from about 40%w/w to about 60%w/w, Crospovidone is present in the range from about 0.5 %w/w to about 10% w/w preferably in the range from about 1.5 %w/w to about 7.5%w/w and a combination of Microcrystalline cellulose and maize starch is present in the range from about 15%w/w to about 55%w/w, preferably in the range from about 30%w/w to about 45%w/w. The orally disintegrating tablet further comprises at least one pharmaceutically acceptable excipient selected from Acesulfame potassium, 1-Tydroxypropyl cellulose, Poloxamer 407 and Magnesium Stearate.
As per one embodiment of the present invention, the ratio of diluent to di sintegrant is in the range of 10:1 to 15:1 and preferably it is in the range of 12:1 to 14:1. As per preferred embodiment of the present invention, the ratio of combination of Microcrystalline cellulose and Maize Starch to Crospovidone is in the range of 10:1 to 15:1 and preferably it is in the range of 12:1 to 14: 'Increase in amount of disintegrant Crospovidone caused a decrease in disintegration time whereas amount of maize starch was changed in different batches and microcrystalline cellulose was kept constant The ratio of microcrystalline cellulose and maize starch to Crospovidone is optimized in order to achieve fast disintegration of tablet.
As per one embodiment of the present invention, the process for the preparation of orally disintegrating tablets containing Gabapentin or salts thereof, by direct compression method which is one of the most economical methods. The direct compression method is primarily used as it requires fewer processing steps and less equipment. Therefore, the method is potentially less expensive than other methods used in tablet manufacture.
As per one embodiment of the present invention, the disintegrating time of the Gabapentin orally disintegrating tablet is not more than 3 minutes, preferably less than 50 seconds.
As per one embodiment of the present invention, more than 90% of the Gabapentin is released in 15 minutes, preferably more than 90% is released within 10 minutes.
As per one embodiment of the present invention, packaging material for Orally disintegrating tablet of Gabapentin is selected from the Polypropylene Bottle with Silica canister, PP Bottle with Oxygen scavenger, HDPE Bottle, HDPE Bottle with Silica canister, HDPE Bottle with Oxygen scavenger, Alu-Alu Blister. In present invention, the HDPE Bottle with silica canister is preferred as packaging material over other packaging materials as it provided desired physical parameters like appearance of tablets and desired chemical parameters like lesser impurities on storage for 3 months.
As per one embodiment of the present invention, the orally disintegrating tablet of Gabapentin can be effective in the treatment of postherpetic neuralgia and various types of peripheral neuropathic pain, such as painful diabetic neuropathy in adults and partial-onset seizures in paediatrics.
As per one embodiment of the present invention, the orally disintegrating tablet is manufactured by direct compression. Gabapentin, maize starch, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, Poloxamer 407 and acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieve separately through 60# sieve. Sifted quantity of Gabapentin, maize starch was mixed properly for 15 minutes in blender. To this powder mixture, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, acesulfame potassium and poloxamer 407 were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets. The prepared tablets were packed in HDPE Bottles with silica canister as it provided good physical parameters and chemical parameters like impurities were found to be lesser as compared to other packaging materials in stability studies for 3 months.
The invention is further illustrated by the following examples, which are by no means intended to limit the scope of the invention but are given by way of illustration.
Example 1:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table-I for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE-I
Manufacturing process: Gabapentin, microcrystalline cellulose, maize starch, crospovidone and Acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieved separately through 60# sieve. Sifted quantity of gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture, sifted quantity of crospovidone, microcrystalline cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium Gabapentin 54.5 Maize Starch 15.9 Microcrystalline cellulose 26.8 Crospovidone 1.8 Acesulfame potassium 0.3 Magnesium stearate 0.7 Total stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes Finally, the lubricated mixture is compressed to form tablets.
Weight variation observed due to poor blend flow. In order to optimize blend flow, it was necessary to increase the concentration of Lubricant.
Example 2:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table II for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE -II
Bulk Density (gm/m1) 0.4475 Tap Density (gm/m1) 0.6712 Carr Index (/o) 33.33 Hausner Ratio 1.50 :MiM=UMN:M=MM JiatitioreffiellItcaaa Gabapentin 54.5 Maize Starch 15.5 Microcrystalline cellulose 26.8 Crospovidone 1.8 Acesulfame potassium 0.3 Magnesium stearate 1.1 Total 100.0 Manufacturing process: Gabapentin, mi crocry stall i ne cellulose, maize starch, crospovi done, and acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieved separately through 60# sieve. Sifted quantity of Gabapentin, Maize starch were mixed properly for 15 minutes in blender. To this powder mixture, crospovidone, microcrystalline cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium stearate to the pre-lubricated blend was added and mixed in a blender for 5 minutes. Finally; the lubricated mixture is compressed to form tablets.
Flow properties increased but tablet lamination observed during compression. In order to remove lamination issue, it was necessary to add Hydroxypropyl Cellulose as a dry binder.
Bulk Density (gm/ml) 0.4320 Tap Density (gm/m1) 0.5865 Carr Index (%) 26.34 Hausner Ratio 1.35
Example 3:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table Ell for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE -III
Gabapentin 54.5 Maize Starch 14.58 MicrocrystaIline cellulose 26.8 Crospovidone 1.8 Acesulfame potassium 0.3 Hydroxypropyl Cellulose 0.9 Magnesium stearate 1.1 Total 100.0 Manufacturing process: Gabapentin, microcrystalline cellulose, maize starch, crospovidone, hydroxypropyl cellulose and acesulfame potassium were sieved separately through 40# sieve.
Magnesium Stearate was sieved separately through 60# sieve. Sifted quantity of Gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture microcrystalline cellulose, crospovidone, hydroxypropyl cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets.
Still minor tablet lamination was observed. In order to minimize lamination issue, it was necessary to increase concentration of Hydroxypropyl cellulose.
Example 4:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table W for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE -IV
Gabapentin 54.5 Maize Starch 13.67 Microcrystalline cellulose 26.8 Crospovidone 1.8 Acesulfame potassium 0.3 Hydroxypropyl Cellulose 1.8 Magnesium stearate 1.1 Total 100.0 Manufacturing process: Gabapentin, microcrystalline cellulose, Maize starch, crospovi done, hydroxypropyl cellulose and acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieved separately through 60# sieve. Sifted quantity of gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets Disintegration time observed higher side than usual In order to decrease disintegration time, it was necessary to increase concentration of di sintegrant.
Example 5:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table V for different dose 15 strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE -V g:
Gabapentin 54.5 Maize Starch 12.76 Microcrystalline cellulose 26.8 Crospovidone 2.7 Acesulfame potassium 0..3 Hydroxypropyl Cellulose 1.8 Magnesium stearate 1.1 Total 100.0 Manufacturing process: Gabapentin, microcrystalline cellulose, maize starch, crospovidone, hydroxypropyl cellulose and acesulfame potassium were sieved separately through 40# sieve.
Magnesium Stearate was sieve separately through 60# sieve. Sifted quantity of gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture Microcrystalline cellulose, crospovidone, microcrystalline cellulose, hydroxypropyl cellulose and acesulfame potassium were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets.
All the physical parameters of tablets were found to be satisfactory but chemical parameters of tablets were found not satisfactory after 1-month stability data of Related Substances. In order to stabilize formulation during stability, it was necessary to add stabilizer as a Poloxamer 407.
Bulk Density (gm/ml) 0.4130 Tap Density (gm/me 0.5531 Carr Index (%) 25.32 Hausner Ratio 1.33
Example 6:
The Orally disintegrating tablet was made according to the method defined below using the formulation having the ingredients shown in table VI for different dose strengths that are 100 mg, 300mg, 400mg, 600mg and 800mg of gabapentin:
TABLE-VT
Gabapentin 54.5 Maize starch 10.95 Microcrystalline cellulose 26.73 Crospovidone 2.73 Acesulfame potassium 0.33 Poloxamer 407 1.81 Hydroxy Propyl Cellulose 1.81 Magnesium stearate 1.09 Total 100.0 Manufacturing process: Gabapentin, maize starch, microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, poloxamer 407 and acesulfame potassium were sieved separately through 40# sieve. Magnesium Stearate was sieve separately through 60# sieve. Sifted quantity of gabapentin, maize starch were mixed properly for 15 minutes in blender. To this powder mixture, microcrystalline cellulose, crospovidone, hydroxypropyl Cellulose, acesulfame potassium and poloxamer 407 were added and mixed in blender for 15 minutes and then magnesium stearate was added to the pre-lubricated blend and mixed in a blender for 5 minutes. Finally, the lubricated mixture is compressed to form tablets. The prepared tablets were packed in I1DPE Bottles with silica canister as it provided good physical parameters and chemical parameters like impurities were found to be lesser as compared to other packaging materials in stability studies for 3 months.
All the physical and chemical parameters of tablets were found satisfactory after 3-month stability data as per below results: Bulk Density (gm/m1) 0.4075 Tap Density (gm/m1) 0.5314 Car Index (%) 23.31 Hausner Ratio 1.30 Example 7: The Dissolution profile of the tablet prepared according to
Example 6.
The conditions of dissolution are as following: Product Name: Gabapentin 300 mg orally disintegrating tablet Media: 0.1 N HCI Apparatus & RPM: Apparatus II (Paddle) Rate of rotation: 50 RPM Volume: 900 ml Temperature 37°C Detection: High performance liquid chromatography equipped with UV/PDA Detector at 210 nm The orally disintegrating tablet of Gabapentin was tested for its dissolution profile measured in 900mL of 0.1 N HC1 at 50 RPM in USP II (Paddle) apparatus and active ingredient of the tablet is released in more than 90% in 10 minutes.
Example 8: The orally disintegrating tablets prepared according to example 6 were subjected to a stability study of 25°C/60% RH for 3 months. The stability study was performed for 300 mg dose strength of Gabapentin Results are tabulated below.
Gabapentin 300 mg orally disintegrating tablet Hardness 30N-100N (Target 45N) 46N 38N Average weight 550.0 mg ± 5% (522.5 mg -577.5mg) 552.4mg 551.4mg Thickness 4.50 ± 0.30 mm (4.20mm to 4.80mm) 4.53mm 4.52 mm Friability Not more than 1.0% 0.29% 0.29% Disintegration time Not more than 3 minutes 14 sec 22sec Dissolution NLT 75% (Q) labelled 98.9 97.6 amount of Gabapentin should be dissolve in 15 minutes.
Assay (%) 95.0-105.0 % 100.0 101.4 Impurities (%)
RS-A
Impurity A Not more than 0.4% 0.051 0.0572 Single maximum Not more than 0.1% ND ND unknown impurity
RS-B
Single maximum Not more than 0.05% ND ND unknown impurity Total impurities for RS-A and RS-B Not more than 1.0% 0.051 0.0572
Claims (1)
- Claims: 1.An orally disintegrating tablet of Gabapentin for oral administration comprising: a) Gabapentm or pharmaceutically acceptable salts thereof, present in the range of about 30%w/w to about 70%w/w, preferably in the range from about 40%w/w to about 5 60%w/w; b) at least one diluent; c) at least one disintegrant present in the range from about 0.5%w/w to about 10.0%w/w, preferably in the range from about 1.5%w/w to about 7.5%w/w; and d) at least one stabilizer present in the range from about 0.5 %w/w to about 3.0 %w/w, 10 preferably in the range of about I.0%w/w to about 2.0 %w/w.2.The orally disintegrating tablet according to claim 1, wherein the diluent is selected from the group consisting of spray-dried lactose, dicalcium phosphate, dextrates, microcrystalline cellulose, dextrose, maize starch, fructose, sorbitol, pregelatinized starch, starch, xylitol, sucrose, sorbitol, maltodextrin, maltose, mannitol or combinations thereof 3.The orally disintegrating tablet according to claim 2, wherein the diluent is microcrystalline cellulose present in the range from about 15%w/w to about 50%w/w, preferably in the range from about 20%w/w to about 40%w/w.4.The orally disintegrating tablet according to claim 2, wherein at least 30% of the total weight of microcrystalline cellulose has an average particle size in the range from about pm to about 100 tm, preferably in the range from about 90 i.irn to about 100 [Lin and the bulk density is in the range from about 0.26g/m1 to about 0.34g/ml, preferably in the range from 0.30g/m1 to about 0.33g/ml.5.The orally disintegrating tablet according to claim 2, wherein at least 70% of the total weight of microciystalline cellulose has a particle size lesser than 75 gm, preferably lesser than 70 gm and the bulk density is in the range from about 0.10 g/cm3 to about 0.15 g/cm3, preferably from about 0.11 g/cm3 to about 0.14g/cm3.6.The orally disintegrating tablet according to claim 2, wherein the diluent is Maize Starch present in the range from about 5%w/w to about 30%w/w, preferably in the range from about 7 %w/w to about 25 %w/w.7.The orally disintegrating tablet according to claim 1, wherein the diluent is the combination of microcrystalline cellulose and Maize starch present in the range from 10 about 15%w/w to about 55 %w/w, preferably in the range from about 30% w/w to about 45%w/w.8.The orally disintegrating tablet according to claim 1, wherein the disintegrant is selected from the group consisting of modified starches, cross-linked polyvinylpyrrolidone, croscarmellose sodium, soy polysaccharide, cross-linked alginic acid, gellan gum, calcium silicate or combinations thereof 9.The orally disintegrating tablet according to claim 8, wherein the disintegrant is Crospovidone.10.The orally disintegrating tablet according to claim 1, wherein the stabilizer is selected from the group consisting of Poloxamers, Amino acid-based stabilizers, sodium alginate, sodium carboxymethyl cellulose (CMC), guar gum, locust bean gum, carrageenan, gelatin, and pectin, Povidone, Polyvinyl alcohol, Sodium lauryl sulfate or combinations thereof.11 The orally disintegrating tablet according to claim 10, wherein the stabilizer is Poloxamer 407.12.The orally disintegrating tablet according to claim 1, wherein pharmaceutical composition further comprises at least one or more pharmaceutically acceptable excipients are selected from the group consisting of binders, sweeteners, and lubricants or combinations thereof 13.The orally disintegrating tablet according to claim 12, wherein the lubricant is selected from the group consisting of boric acid, magnesium stearate, Sodium Stearyl fumarate, micronized poly oxy ethylene glycol, leucine, sodium benzoate, sodium acetate, sodium lauryl sulfate, stearic acid, sodium stearate, sodium oleate, Poloxamer 407, calcium stearate, waxes or combinations thereof.14.The orally disintegrating tablet according to claim 12, wherein the lubricant is Magnesium Stearate is present in the range from about 0.5%w/w to about 4.5%w/w, preferably in the range from about 1.0%w/w to about 2.5%w/w.15.The orally disintegrating tablet according to claim 12, wherein the binder is selected from the group consisting of alginic acid, carbomer, ethyl cellulose, gelatin, glucose, guar gum, hydroxy ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methyl cellulose, polydextrose, polyethylene oxide, and Povidone K30 or combinations thereof.16.The orally disintegrating tablet according to claim 12, wherein the binder is hydroxypropyl cellulose present in the range from about 0.5% w/w to about 6.0% w/w, preferably in the range from about 1 %w/w to about 3 %w/w.17.The orally disintegrating tablet according to claim 12, wherein the sweetener is selected from the group consisting of cyclamate, acesulfame potassium, neo hesperidin dihydrochalcone, monoammonium glycyrrhizinate, saccharin sodium, sucralose, saccharin, aspartame or combinations thereof.18.The orally disintegrating tablet according to claim 12, wherein the sweetener is acesulfame potassium present in the range from about 0.05 %w/w to about 2 %w/w, preferably in the range from about 0.30 %w/w to about 1.5 %w/w.I 9.The orally disintegrating tablet according to claim I, further comprises magnesium stearate, hydroxypropyl cellulose, Acesulfame potassium, and Crospovidone.20.The orally disintegrating tablet according to claim 1, wherein the ratio of a diluent to disintegrant is in the range of 10:1 to 15:1 and preferably in the range of 12:1 to 14:1.21 The orally disintegrating tablet according to claim I, wherein the orally disintegrating tablet is manufactured by the direct compression method comprising the steps of (a)Sieving separately Gabapentin, microcrystalline cellulose, maize starch, crospovidone, Hydroxy Propyl Cellulose, Poloxamer 407, and Acesulfame potassium through 40# sieve and magnesium Stearate separately through 60# sieve: (b)Mixing of the previously sifted quantity of gabapentin and Maize starch for 15 minutes in a blender; (c)Blending the sifted quantity of microcrystalline cellulose, crospovidone, hydroxy propyl cellulose, poloxamer 407, and Acesulfame potassium in the blender with step-(b) for 15 minutes in blender; (d) Adding magnesium stearate to the pre-lubricated blend of step-(c) in a blender for 5 minutes; (e) Compressing the resulting mixture into a tablet; and (f) packing of the tablet into HDPE Bottles with silica canister.22. The orally disintegrating tablet according to claim 1, wherein the orally disintegrating tablet is disintegrated in the buccal cavity upon contact with saliva in less than 3 minutes, preferably less than 50 seconds 23. The orally disintegrating tablet according to claim I, is for the treatment or prevention of postherpetic neuralgia and various types of peripheral neuropathic pain such as painful diabetic neuropathy in adults and partial-onset seizures in pediatrics.24. The orally disintegrating tablet according to claim I, wherein the packaging material of the container is selected from the Polypropylene Bottle with Silica canister, PP Bottle with Oxygen scavenger, 1-1DPE Bottle, 1-1TWE Bottle with Silica canister, HOPE. Bottle with Oxygen scavenger, Alu-Alu Blister.25. The orally disintegrating tablet according to claim 24, wherein the tablet is more stable for at least three months at 25°C and 60% relative humidity in HOPE Bottle with a Silica canister.
Priority Applications (2)
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| GB2219356.9A GB2625579A (en) | 2022-12-21 | 2022-12-21 | An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same |
| PCT/GB2023/053353 WO2024134210A1 (en) | 2022-12-21 | 2023-12-21 | An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same |
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| GB2219356.9A GB2625579A (en) | 2022-12-21 | 2022-12-21 | An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020012679A1 (en) * | 1998-08-03 | 2002-01-31 | Societe Laboratoires Des Produits Ethiques - Ethypharm | Process for manufacturing coated gabapentin or pregabalin particles |
| WO2004089343A1 (en) * | 2003-04-09 | 2004-10-21 | Ranbaxy Laboratories Limited | Water soluble tablets |
| CN101305987A (en) * | 2007-05-17 | 2008-11-19 | 北京利乐生制药科技有限公司 | Compound gabapentin mecobalamin dispersible tables and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2460891C2 (en) | 1974-12-21 | 1982-09-23 | Gödecke AG, 1000 Berlin | 1-aminomethyl-1-cycloalkaneacetic acids and their esters, processes for their preparation and medicaments containing these compounds |
| WO2003103634A1 (en) | 2002-06-07 | 2003-12-18 | Ranbaxy Laboratories Limited | Sustained release oral dosage forms of gabapentin |
| WO2004032905A1 (en) | 2002-10-08 | 2004-04-22 | Ranbaxy Laboratories Limited | Gabapentin tablets and methods for their preparation |
| ITMI20041447A1 (en) | 2004-07-20 | 2004-10-20 | Zambon Spa | PHARMACEUTICAL COMPOSITION INCLUDING GABAPENTINA |
| US20090176882A1 (en) | 2008-12-09 | 2009-07-09 | Depomed, Inc. | Gastric retentive gabapentin dosage forms and methods for using same |
| ES2288117B1 (en) * | 2006-05-08 | 2008-12-01 | Combino Pharm, S.L. | SOLID PHARMACEUTICAL COMPOSITION OF GABAPENTINA. |
| WO2015144825A1 (en) | 2014-03-27 | 2015-10-01 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Oral liquid pharmaceutical solution of gabapentin |
-
2022
- 2022-12-21 GB GB2219356.9A patent/GB2625579A/en active Pending
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2023
- 2023-12-21 WO PCT/GB2023/053353 patent/WO2024134210A1/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020012679A1 (en) * | 1998-08-03 | 2002-01-31 | Societe Laboratoires Des Produits Ethiques - Ethypharm | Process for manufacturing coated gabapentin or pregabalin particles |
| WO2004089343A1 (en) * | 2003-04-09 | 2004-10-21 | Ranbaxy Laboratories Limited | Water soluble tablets |
| CN101305987A (en) * | 2007-05-17 | 2008-11-19 | 北京利乐生制药科技有限公司 | Compound gabapentin mecobalamin dispersible tables and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| Pharmaceutical development and technology, vol. 25, no. 2, 2019, Soliman, I. et al., "Gabapentin-saccharin co-crystals with enhanced physicochemical properties and in vivo absorption formulated as oro-dispersible tablets.", p. 227-236. * |
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| WO2024134210A1 (en) | 2024-06-27 |
| GB202219356D0 (en) | 2023-02-01 |
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