Self-emulsifying formulation of bisphosphonates and associated dosage forms

Abstract

The patent discloses self-emulsifying formulations of bisphosphonates or bisphosphonic acids in the prevention and treatment of conditions involving calcium or phosphate metabolism. The dosage forms are either capsules, or tablets, or other controlled release drug delivery systems, or devices that contain self-emulsifying formulation of such bisphosphonates or bisphosphonic acids.

Description

TECHNICAL FIELD[0001]The present invention relates to drug delivery of novel self-emulsifying formulations of bisphosphonates or bisphosphonic acids. The invention additionally relates to dosage forms using the disclosed self-emulsifying drug delivery system.BACKGROUND[0002]Bisphosphonates or “bisphosphonic acids” are used in the diagnosis and treatment of disorders and conditions related to bone resorption, calcium metabolism and phosphate metabolism, including, but not limited to, osteoporosis, Paget's disease, periprosthetic bone loss or osteolysis, metastatic bone disease, hypercalcemia of malignancy, multiple myeloma, periodontal disease, and tooth loss. These compounds include 1-hydroxyethane-1,1-diphosphonic acid (etidronic acid, salts of which are referred to as “etidronate”), 1,1-dichloromethylene-1,1-bisphosphonic acid (clodronic acid, salts of which are is referred to as “clodronate”), 3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid (pamidronic acid, salts of which ar...

AI Technical Summary

Benefits of technology

[0015]Published literature has focused on preparing solid or semi-solid formulations that discharge bisphosphate into digestive tracts directly when mixed with gastric or intestine fluid. No one has reported a self-emulsifying formulation of bisphosphonate complex that undergoes a spontaneous phase transition in contact with gastric or intestinal fluid and thereafter self-emulsification. The phase transition allows the complexed active agent to remain embedded in emulsion vesicles and slowly discharge into bulk medium such as gastric or intestine fluid. Self-emulsifying formulation and controlled release system modify the interaction between active agent and digestive tract, which in turn lessens undesirable irritation as seen in other formulations and potentially improves drug bioavailability.

[0016]Accordingly, it is a primary object of the invention to address the above-mentioned need in the art by providing self-emulsifying formulations to potentially improve bioavailability of bisphosphonates or bisphosphonic acid compounds.

[0017]It is another object of the invention to provide a dosage form for the administration of bisphosphonates or bisphosphonic acid compounds in self-emulsifying formulations to potentially avoid GI side effects.

Problems solved by technology

Although the bisphosphonates or bisphosphonic acids are therapeutically effective, oral administration of the drugs is problematic, primarily because of adverse gastrointestinal effects, particularly irritation of the esophagus.

Even with risedronate, which can be administered at relatively low doses because of its potency, many patients still complaint heartburn and esophageal burning.

All of these characteristics contribute to the problem of very low oral bioavailability for the bisphosphonates or bisphosphonic acids.

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