A NOVEL TRANSMUCOSAL DELIVERY SYSTEM
Technical Field
• The present invention relates to use of uncoated benzimidazole derivative in the form of an oral mucoadhesive tablet dosage form for sublingual, buccal, gingival administration to suppress gastric acid secretion by inhibition of the proton pump at the secretory surface of gastric parietal cells. Background of the inventions
Benzimidazole class of PPI, that inhibit gastric acid secretion are typically available as enteric coated tablets, pellets or granules or orally disintegrating tablet consisting of enteric coated drug.
The use of enteric coating of the drug is essential as this class of drugs are prone
to acid degradation. Manufacturing process for enteric coated pellets and tablets is
lengthy and cumbersome. Also, the absorption and thereby onset of action of the drug is
delayed. There is also food effect in the absorption of the drug. The drugs also undergo
extensive hepatic first pass metabolism.
For acute and chronic cases of gastric ulcer, duodenal ulcers, GERD, severe
erosive oesophagitis and other pathological hypersecretory conditions such as Zollinger
Ellison syndrome, a fast acting dosage form is the purpose of the invention. "•' US patents 6,498,171, 6,328,993,6365184 and 6,296,876 covers enteric coating
of PPI class of drugs.
US patent 6,328,993 claims use of a base, fatty alcohol or mixtures of fatty
alcohols and base to cover active drug units. US patent no. 6489346 covers substituted
alcohols and base to cover active drug units. US patent no. 6489346 covers substituted benzimidazole dosage forms and methods of using uncoated tablets with the use of excess of buffering agents in the range of 01. m.eqύiv. to 2.5 m.equiv. per mg. of. PPI. US patent 63031147 covers bioadhesive solid dosage forms consisting of TLT 80 % pregelatinised starch.
US Patent 5,723,114 describes a method for enhancing penetration of a therapeutic or prophylactic agent and penetration enhancing compositions including transdermal and transmucosal dosage forms.
US Patent applications 20030166553 mentions among other potential pharmaceutical agents and dosage forms, proton pump inhibitors and transmucosal delivery systems.
The present invention have intensively studied the formulation aspect of uncoated
mucosal delivery tablets for achieving appropriate dissolution and stabilizing the dosage
forms. Appropriate formulation studies also have been done by the inventors to achieve.
palatability and patient's acceptance for these delivery systems. . •
According to the present invention, a method of producing mucosal delivery
drugs is outlined below wherein the drug Lansoprazole is either mixed in directly
compressible ingredients or granules of. the same are manufactured using wet
granulation methods. Lactose, MCC, mannitol, sucrose or glucose were used as directly compressible
vehicle and sodium bicarbonate, di sodium hydrogen orthophosphate, magnesium
carbonate, lysine, glycine and sodium hydroxide as stabilizer. Sodium Lauryl sulphate,
croscarmellose sodium, crospovidone, SSG, indion (resin) were used to achieve appropriate disintegration. Sodium stearyl fumarate is used as lubricant. . Detailed Description of the invention:
The present invention relates to use of PPI' s in the uncoated form which is to be administered in oral cavity e.g. sublingual, gingival.
The invention also describes the dosage form which overcomes the destabilizing effect of PPI's by gastric juice and avoids extensive hepatic metabolism commonly encounters with this class of drugs after oral administration.
The transmucosal DDS of the present invention will also help in reducing the
onset of action and reduce dosage requirement.
For this invention, the term PPI (Proton Pump Inhibitors), shall mean any
benzimidazole class of PPI used as proton pump inhibitors. The inventive composition
comprises sublingual or other oral mucosal delivery system produced by either dry
granulation, wet granulation or direct compression method, After absorption through oral mucosal layer, drug is available to various tissues
through blood stream including parietal cells to elicit the desired pharmacological
actions.
A pharmaceutical formulation can be administered by keeping the dosage form
under the tongue (sublingual) or under the lips (gingival), or between the cheek and
gum (buccal) to aid absorption through oral mucosa without swallowing! .
Examples :. T IN2004/000013
Preparation of Tablets by Direct Compression Method
Preparation of Tablets by Dry Granulation Method
Preparation of Tablets by Wet Granulation Method
Manufacturing Process .Lansoprazole was mixed with Di Sodium Hydrogen Orthophosphate or Sodium Bicarbonate, Mannitol, Glucose Monohydrate and MCC PH 102. The blend was granulated with PVP K30 solution in Purified Water and Special Denatured Spirit in ratio of 1:1 The wet granules were dried in Tray dryer. The dried granules were mixed with lubricants and compressed into the tablets.
Preparation of Omeprazole Magnesium Tablets by Wet Granulation Methoc
Preparation of Omeprazole Magnesium Tablets by Direct Compression Method.
Preparation oi meprazoie iviagnesium ιaυιcι> υy wci «• ««■
*.« nw« ITJL I
Preparation of Omeprazole Magnesium Tablets by Direct Compression Method.
Preparation of Pantoprazole Sodium Tablets by Wet Granulation Method.
Preparation of Pantoprazole Sodium Tablets by Direct Compression Method.
Sr. Ingredients Example 4 Example 5 Example 6 No. % w/w . . % w/w :■: % W/W Pantoprazole Sodium 14.1 14.1 14.1 Sesquihydrate Mannitol (Free Flow) 62 62 62 Di Sodium Hydrogen Orthophosphate Hydroxypropylcellulose 1.33 1.33 1.33 Sodium Stearyl Fumarate 1.33 1.33 1.33 Sodium Starch Glycolate 13.34
7 Croscarmellose Sodium 13.34 Crospovidone T3.3 Talc
10 Aspartame 1.23 1.23 1.23
11 Flavor 0.67 0.67 0.67 Hardness 2 to 5 kp 2 to 5 kp. 2 to 5 kp Disintegration Time 3 min 45 2 min 45. 2 min 30 sec sec . sec
Manufacturing Process: Pantoprazole . Sodium Sesquihydrate was mixe with Di Sodium Hydrogen Orthophosphate, Mannitol and Hydroxypropylcellulose. The blend was further blended with Sodium Stearyl Fumarate, Talc, Aspartame, Sodium Starch Glycolate or Croscarmellose Sodium or Crospovidone and Flavor. . The lubricated granules were compressed, into tablets.
Preparation of Pantoprazole Sodium Tablets by Wet Granulation Method.
Preparation of Pantoprazole Sodium Tablets by Wet Granulation Method.
Preparation of Rabeprazole Sodium Tablets by Direct Compression Method.
1 Preparation of Rabeprazole Sodium Tablets by Wet Granulation Methoc
Preparation of Rabeprazole Sodium Tablets by Wet Granulation Method.
Preparation of Rabeprazole Sodium Tablets by Direct Compression Method.
While the present invention is described
' above in connection with, preferred or illustrative embodiments, these embodiments are not intended to- be exhaustive or limiting of the invention. Rather, the invention is intended to cover all alternatives, modifications and equivalents included within its. spirit and scope, as defined by appended claims.