Description:FIELD OF DISCLOSURE
[0001] The present disclosure relates generally relates to the pharmaceutical field. More specifically, it pertains to a method for development and evaluation of colchicine eutectogel for gout disease.
BACKGROUND OF THE DISCLOSURE
[0002] Gout is a common and complex form of arthritis characterized by sudden, severe attacks of pain, swelling, redness, and tenderness in the joints, particularly at the base of the big toe.
[0003] The condition is caused by the deposition of monosodium urate crystals in the joints, which occurs due to elevated levels of uric acid in the blood. The management of gout primarily involves the reduction of uric acid levels, pain relief during acute attacks, and long-term prevention of future episodes.
[0004] Colchicine, a natural alkaloid derived from the plant Colchicum autumnale, has been widely used for the treatment and prophylaxis of gout. Colchicine acts by inhibiting microtubule polymerization, which, in turn, reduces the inflammatory response caused by the deposition of urate crystals in the joints.
[0005] However, the use of colchicine is associated with several limitations, including gastrointestinal disturbances, narrow therapeutic index, and potential toxicity at higher doses. Moreover, the conventional oral formulations of colchicine may lead to systemic side effects and reduced patient compliance due to the need for frequent dosing.
[0006] The preparation of a eutectogel involves a complex formulation process, requiring precise control over the ratio of components, temperature, and mixing conditions. This complexity can lead to variability in the final product, affecting its consistency and efficacy.
[0007] Colchicine, being a sensitive molecule, may face stability issues when incorporated into a eutectogel. The interaction between the active pharmaceutical ingredient (API) and the eutectic system might cause degradation over time, leading to reduced therapeutic effectiveness.
[0008] As a topical formulation, there is a risk of skin irritation or allergic reactions in patients, especially if the eutectogel contains certain excipients that may not be well-tolerated by all users. This could limit its widespread use.
[0009] While eutectogels are designed to enhance drug delivery through the skin, the penetration depth and rate of colchicine may still be insufficient for achieving therapeutic levels in deeper tissues, potentially reducing its effectiveness in treating gout.
[0010] Scaling up the production of colchicine eutectogel from laboratory to industrial scale can pose significant challenges. Ensuring uniformity, maintaining quality control, and meeting regulatory standards may require advanced manufacturing techniques, increasing production costs.
[0011] Introducing a novel formulation like a colchicine eutectogel may face stringent regulatory scrutiny, particularly concerning its safety, efficacy, and quality. Meeting these regulatory requirements can be time-consuming and costly, potentially delaying its market entry.
[0012] Although topical formulations are generally preferred for their ease of use, patient compliance may still be an issue if the eutectogel requires frequent application or has an unpleasant texture, odour, or colour.
[0013] The development of a colchicine eutectogel, involving specialized ingredients and advanced technology, may result in a higher cost compared to conventional gout treatments. This could limit its accessibility and affordability for patients.
[0014] Thus, in light of the above-stated discussion, there exists a need for a method for development and evaluation of colchicine eutectogel for gout disease.
SUMMARY OF THE DISCLOSURE
[0015] The following is a summary description of illustrative embodiments of the invention. It is provided as a preface to assist those skilled in the art to more rapidly assimilate the detailed design discussion which ensues and is not intended in any way to limit the scope of the claims which are appended hereto in order to particularly point out the invention.
[0016] According to illustrative embodiments, the present disclosure focuses on a method for development and evaluation of colchicine eutectogel for gout disease which overcomes the above-mentioned disadvantages or provide the users with a useful or commercial choice.
[0017] An objective of the present disclosure is to develop a eutectogel formulation of colchicine for the effective treatment of gout disease.
[0018] Another objective of the present disclosure is to evaluate the physicochemical properties of the colchicine eutectogel, including stability, viscosity, and drug release profile.
[0019] Another objective of the present disclosure is to assess the in vitro and in vivo efficacy of the colchicine eutectogel in reducing inflammation and pain associated with gout.
[0020] Another objective of the present disclosure is to compare the therapeutic performance of the colchicine eutectogel with existing formulations in terms of bioavailability and patient compliance.
[0021] Another objective of the present disclosure is to ensure the colchicine eutectogel is safe for topical application by conducting toxicity and skin irritation studies.
[0022] Another objective of the present disclosure is to optimize the formulation process to achieve a consistent and reproducible colchicine eutectogel with desired therapeutic effects.
[0023] Another objective of the present disclosure is to assess the in vitro and in vivo efficacy of the colchicine eutectogel in reducing inflammation and pain associated with gout disease.
[0024] Another objective of the present disclosure is to optimize the formulation parameters for the colchicine eutectogel to ensure maximum bioavailability and therapeutic effectiveness.
[0025] Another objective of the present disclosure is to investigate the safety profile of the colchicine eutectogel through toxicological studies and biocompatibility tests.
[0026] Yet another objective of the present disclosure is to compare the therapeutic outcomes of the colchicine eutectogel with conventional gout treatment methods.
[0027] In light of the above, a method for development and evaluation of colchicine eutectogel for gout disease comprises identifying and selecting colchicine as the active pharmaceutical ingredient for the treatment of gout disease. The method includes formulating a eutectic mixture by combining colchicine with one or more suitable excipients. The method also includes incorporating the prepared eutectic mixture into a gel base. The method also includes evaluating the physical and chemical properties of the eutectogel. The method also includes conducting an in-vitro release study to assess the drug release profile of colchicine from the eutectogel. The method also includes performing preclinical and/or clinical evaluations of the colchicine eutectogel to assess its therapeutic efficacy in the treatment of gout disease. The method also includes refining the formulation based on the results of the characterization and evaluation studies to achieve an optimal balance of drug release, stability, and therapeutic efficacy. The method also includes defining a scalable manufacturing process for the colchicine eutectogel.
[0028] In one embodiment, the colchicine is selected in a pharmaceutically acceptable salt form to enhance its solubility and stability in the eutectogel formulation.
[0029] In one embodiment, the suitable excipients used in the eutectic mixture include sugars.
[0030] In one embodiment, the suitable excipients used in the eutectic mixture include alcohols.
[0031] In one embodiment, the suitable excipients used in the eutectic mixture include organic acids.
[0032] In one embodiment, the chemical properties evaluated include the drug content uniformity, ensuring that colchicine is uniformly distributed throughout the eutectogel.
[0033] In one embodiment, the in-vitro release study is conducted using a synthetic membrane to simulate skin permeability and assess the rate and extent of colchicine release from the eutectogel.
[0034] In one embodiment, the in-vitro release study involves the use of a Franz diffusion cell apparatus to provide controlled conditions for the assessment of drug release kinetics.
[0035] In one embodiment, the therapeutic efficacy of the colchicine eutectogel is evaluated in preclinical animal models of gout disease, including assessments of reduction in inflammation and pain.
[0036] In one embodiment, the clinical evaluations include a double-blind, placebo-controlled study to assess the safety and efficacy of the colchicine eutectogel in human subjects with gout disease.
[0037] These and other advantages will be apparent from the present application of the embodiments described herein.
[0038] The preceding is a simplified summary to provide an understanding of some embodiments of the present invention. This summary is neither an extensive nor exhaustive overview of the present invention and its various embodiments. The summary presents selected concepts of the embodiments of the present invention in a simplified form as an introduction to the more detailed description presented below. As will be appreciated, other embodiments of the present invention are possible utilizing, alone or in combination, one or more of the features set forth above or described in detail below.
[0039] These elements, together with the other aspects of the present disclosure and various features are pointed out with particularity in the claims annexed hereto and form a part of the present disclosure. For a better understanding of the present disclosure, its operating advantages, and the specified object attained by its uses, reference should be made to the accompanying drawings and descriptive matter in which there are illustrated exemplary embodiments of the present disclosure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] To describe the technical solutions in the embodiments of the present disclosure or in the prior art more clearly, the following briefly describes the accompanying drawings required for describing the embodiments or the prior art. Apparently, the accompanying drawings in the following description merely show some embodiments of the present disclosure, and a person of ordinary skill in the art can derive other implementations from these accompanying drawings without creative efforts. All of the embodiments or the implementations shall fall within the protection scope of the present disclosure.
[0041] The advantages and features of the present disclosure will become better understood with reference to the following detailed description taken in conjunction with the accompanying drawing, in which:
[0042] FIG. 1 illustrates a flowchart outlining sequential step involved in a method for development and evaluation of colchicine eutectogel for gout disease, in accordance with an exemplary embodiment of the present disclosure.
[0043] Like reference, numerals refer to like parts throughout the description of several views of the drawing.
[0044] The method for development and evaluation of colchicine eutectogel for gout disease, which like reference letters indicate corresponding parts in the various figures. It should be noted that the accompanying figure is intended to present illustrations of exemplary embodiments of the present disclosure. This figure is not intended to limit the scope of the present disclosure. It should also be noted that the accompanying figure is not necessarily drawn to scale.
DETAILED DESCRIPTION OF THE DISCLOSURE
[0045] The following is a detailed description of embodiments of the disclosure depicted in the accompanying drawings. The embodiments are in such detail as to communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure.
[0046] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the embodiments of the present disclosure. It may be apparent to one skilled in the art that embodiments of the present disclosure may be practiced without some of these specific details.
[0047] Various terms as used herein are shown below. To the extent a term is used, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
[0048] The terms “a” and “an” herein do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced items.
[0049] The terms “having”, “comprising”, “including”, and variations thereof signify the presence of a component.
[0050] Referring now to FIG. 1 to describe various exemplary embodiments of the present disclosure. FIG. 1 illustrates a flowchart outlining sequential step involved in a method for development and evaluation of colchicine eutectogel for gout disease, in accordance with an exemplary embodiment of the present disclosure.
[0051] A method for development and evaluation of colchicine eutectogel for gout disease 100 comprises identifying and selecting colchicine as the active pharmaceutical ingredient 102 for the treatment of gout disease. The colchicine is selected in a pharmaceutically acceptable salt form 102 to enhance its solubility and stability in the eutectogel formulation.
[0052] The method includes formulating a eutectic mixture by combining colchicine 104 with one or more suitable excipients. The suitable excipients used in the eutectic mixture include sugars. The suitable excipients used in the eutectic mixture include alcohols. The suitable excipients used in the eutectic mixture include organic acids.
[0053] The method also includes incorporating the prepared eutectic mixture into a gel base 106.
[0054] The method also includes evaluating the physical and chemical properties of the eutectogel 108. The chemical properties evaluated include the drug content uniformity 108, ensuring that colchicine is uniformly distributed throughout the eutectogel.
[0055] The method also includes conducting an in-vitro release study 110 to assess the drug release profile of colchicine from the eutectogel. The in-vitro release study is conducted using a synthetic membrane 110 to simulate skin permeability and assess the rate and extent of colchicine release from the eutectogel. The in-vitro release study 110 involves the use of a Franz diffusion cell apparatus to provide controlled conditions for the assessment of drug release kinetics.
[0056] The method also includes performing preclinical and/or clinical evaluations of the colchicine eutectogel 112 to assess its therapeutic efficacy in the treatment of gout disease. The therapeutic efficacy of the colchicine eutectogel 112 is evaluated in preclinical animal models of gout disease, including assessments of reduction in inflammation and pain. The clinical evaluations 112 include a double-blind, placebo-controlled study to assess the safety and efficacy of the colchicine eutectogel in human subjects with gout disease.
[0057] The method also includes refining the formulation based on the results of the characterization and evaluation studies 114 to achieve an optimal balance of drug release, stability, and therapeutic efficacy.
[0058] The method also includes defining a scalable manufacturing process for the colchicine eutectogel 116.
[0059] FIG. 1 illustrates a flowchart outlining sequential step involved in a method for development and evaluation of colchicine eutectogel for gout disease.
[0060] The process begins with the identification and selection of colchicine as the active pharmaceutical ingredient (API). Colchicine is chosen due to its established efficacy in treating gout by reducing inflammation and pain. This step is critical as the choice of API dictates the subsequent formulation processes, ensuring that the therapeutic objectives are met effectively.
[0061] Once colchicine is selected, the next step involves the formulation of a eutectic mixture. Colchicine is combined with one or more suitable excipients, which could include sugars, alcohols, or organic acids. These excipients are chosen based on their ability to create a eutectic system that lowers the melting point of colchicine, enhancing its solubility and bioavailability. The creation of this eutectic mixture is a key phase, as it facilitates the incorporation of colchicine into a gel form by improving its physical properties.
[0062] Following the formulation of the eutectic mixture, the next step is to incorporate this mixture into a gel base. The gel base typically comprises biocompatible and bioadhesive polymers such as carbomers, cellulose derivatives, or natural gums. These polymers are selected for their ability to form a stable, homogenous gel that can effectively deliver the colchicine to the target site. The incorporation process ensures that the eutectic mixture is evenly distributed within the gel, resulting in a consistent and effective eutectogel formulation.
[0063] After the eutectogel is formulated, it undergoes a comprehensive evaluation of its physical and chemical properties. This step includes assessing parameters such as pH, viscosity, spreadability, and stability. These evaluations are essential to confirm that the eutectogel meets the necessary criteria for consistency, homogeneity, and shelf-life. The results of these evaluations determine whether the formulation is suitable for further testing and eventual clinical use.
[0064] The next phase involves conducting an in-vitro release study to assess the drug release profile of colchicine from the eutectogel. This study is designed to monitor how colchicine is released over time from the gel matrix, ensuring that it provides a controlled and sustained release. The release profile is crucial in determining the therapeutic effectiveness of the eutectogel, as it impacts the duration and intensity of the drug's action.
[0065] Following the in-vitro studies, preclinical and/or clinical evaluations are performed to assess the therapeutic efficacy of the colchicine eutectogel in treating gout disease. These evaluations typically involve testing the eutectogel in models that simulate the clinical condition, measuring outcomes such as reduction in inflammation, pain relief, and improvement in joint mobility. The efficacy data obtained from these studies is critical for validating the potential of the eutectogel as a treatment option for gout.
[0066] Based on the results of the characterization, in-vitro studies, and clinical evaluations, the formulation may be refined to achieve an optimal balance of drug release, stability, and therapeutic efficacy. This refinement process might involve adjusting the proportions of the excipients or polymers, modifying the manufacturing conditions, or other changes that enhance the overall performance of the eutectogel.
[0067] The final step in the method is defining a scalable manufacturing process for the colchicine eutectogel. This process must be designed to produce the eutectogel consistently at a commercial scale, ensuring that each batch meets the required quality standards. The manufacturing process is developed in compliance with regulatory requirements, taking into consideration factors such as reproducibility, safety, and cost-effectiveness.
[0068] The method includes formulating a eutectic mixture by combining colchicine with one or more suitable excipients. The method also includes incorporating the prepared eutectic mixture into a gel base. The method also includes evaluating the physical and chemical properties of the eutectogel. The method also includes conducting an in-vitro release study to assess the drug release profile of colchicine from the eutectogel. The method also includes performing preclinical and/or clinical evaluations of the colchicine eutectogel to assess its therapeutic efficacy in the treatment of gout disease. The method also includes refining the formulation based on the results of the characterization and evaluation studies to achieve an optimal balance of drug release, stability, and therapeutic efficacy. The method also includes defining a scalable manufacturing process for the colchicine eutectogel.
[0069] In one embodiment, the colchicine is selected in a pharmaceutically acceptable salt form to enhance its solubility and stability in the eutectogel formulation.
[0070] In one embodiment, the suitable excipients used in the eutectic mixture include sugars.
[0071] In one embodiment, the suitable excipients used in the eutectic mixture include alcohols.
[0072] In one embodiment, the suitable excipients used in the eutectic mixture include organic acids.
[0073] In one embodiment, the chemical properties evaluated include the drug content uniformity, ensuring that colchicine is uniformly distributed throughout the eutectogel.
[0074] In one embodiment, the in-vitro release study is conducted using a synthetic membrane to simulate skin permeability and assess the rate and extent of colchicine release from the eutectogel.
[0075] In one embodiment, the in-vitro release study involves the use of a Franz diffusion cell apparatus to provide controlled conditions for the assessment of drug release kinetics.
[0076] In one embodiment, the therapeutic efficacy of the colchicine eutectogel is evaluated in preclinical animal models of gout disease, including assessments of reduction in inflammation and pain.
[0077] In one embodiment, the clinical evaluations include a double-blind, placebo-controlled study to assess the safety and efficacy of the colchicine eutectogel in human subjects with gout disease.
[0078] While the invention has been described in connection with what is presently considered to be the most practical and various embodiments, it will be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the scope of the appended claims.
[0079] A person of ordinary skill in the art may be aware that, in combination with the examples described in the embodiments disclosed in this specification, units and algorithm steps may be implemented by electronic hardware, computer software, or a combination thereof.
[0080] The foregoing descriptions of specific embodiments of the present disclosure have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the present disclosure to the precise forms disclosed, and many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described to best explain the principles of the present disclosure and its practical application, and to thereby enable others skilled in the art to best utilize the present disclosure and various embodiments with various modifications as are suited to the particular use contemplated. It is understood that various omissions and substitutions of equivalents are contemplated as circumstances may suggest or render expedient, but such omissions and substitutions are intended to cover the application or implementation without departing from the scope of the present disclosure.
[0081] Disjunctive language such as the phrase “at least one of X, Y, Z,” unless specifically stated otherwise, is otherwise understood with the context as used in general to present that an item, term, etc., may be either X, Y, or Z, or any combination thereof (e.g., X, Y, and/or Z). Thus, such disjunctive language is not generally intended to, and should not, imply that certain embodiments require at least one of X, at least one of Y, or at least one of Z to each be present.
[0082] In a case that no conflict occurs, the embodiments in the present disclosure and the features in the embodiments may be mutually combined. The foregoing descriptions are merely specific implementations of the present disclosure, but are not intended to limit the protection scope of the present disclosure. Any variation or replacement readily figured out by a person skilled in the art within the technical scope disclosed in the present disclosure shall fall within the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure shall be subject to the protection scope of the claims.
, C , Claims:I/We Claim:
1. A method for development and evaluation of colchicine eutectogel for gout disease (100) comprising:
identifying and selecting colchicine as the active pharmaceutical ingredient (102) for the treatment of gout disease;
formulating a eutectic mixture by combining colchicine (104) with one or more suitable excipients;
incorporating the prepared eutectic mixture into a gel base (106);
evaluating the physical and chemical properties of the eutectogel (108);
conducting an in-vitro release study (110) to assess the drug release profile of colchicine from the eutectogel;
performing preclinical and/or clinical evaluations of the colchicine eutectogel (112) to assess its therapeutic efficacy in the treatment of gout disease;
refining the formulation based on the results of the characterization and evaluation studies (114) to achieve an optimal balance of drug release, stability, and therapeutic efficacy;
defining a scalable manufacturing process for the colchicine eutectogel (116).

2. The system (100) as claimed in claim 1, wherein the colchicine is selected in a pharmaceutically acceptable salt form (102) to enhance solubility and stability in the eutectogel formulation.
3. The system (100) as claimed in claim 1, wherein the suitable excipients used in the eutectic mixture include sugars.
4. The system (100) as claimed in claim 1, wherein the suitable excipients used in the eutectic mixture include alcohols.
5. The system (100) as claimed in claim 1, wherein the suitable excipients used in the eutectic mixture include organic acids.
6. The system (100) as claimed in claim 1, wherein the chemical properties evaluated include the drug content uniformity (108), ensuring that colchicine is uniformly distributed throughout the eutectogel.
7. The system (100) as claimed in claim 1, wherein the in-vitro release study is conducted using a synthetic membrane (110) to simulate skin permeability and assess the rate and extent of colchicine release from the eutectogel.
8. The system (100) as claimed in claim 1, wherein the in-vitro release study (110) involves the use of a Franz diffusion cell apparatus to provide controlled conditions for the assessment of drug release kinetics.
9. The system (100) as claimed in claim 1, wherein the therapeutic efficacy of the colchicine eutectogel (112) is evaluated in preclinical animal models of gout disease, including assessments of reduction in inflammation and pain.
10. The system (100) as claimed in claim 1, wherein the clinical evaluations (112) include a double-blind, placebo-controlled study to assess the safety and efficacy of the colchicine eutectogel in human subjects with gout disease.