WO2021234731A1

WO2021234731A1 - Sustained release compositions

Info

Publication number: WO2021234731A1
Application number: PCT/IN2021/050479
Authority: WO
Inventors: Marina RAJADURAI; Bhavya SUREKHA
Original assignee: Dr Reddy's Institute Of Life Sciences
Priority date: 2020-05-18
Filing date: 2021-05-18
Publication date: 2021-11-25

Abstract

Disclosed herein are compositions for sustained release of an active agent. The compositions comprise an active agent, poly(lactide-co-glycolide) PLGA and one or more additives.

Description

TITLE: SUSTAINED RELEASE COMPOSITIONS

RELATED APPLICATION

This application claims the benefit of Indian provisional application number 202041020828, filed on May 18, 2021; the contents of which are hereby incorporated by reference in their entirety.

TECHNICAL FIELD

The present disclosure relates to compositions that release an active agent (or active ingredient) over an extended period of time.

BACKGROUND

Sustained drug delivery formulations attract large interest due to advantages they can offer, such as improved patient compliance, reduced 'see- saw' fluctuation, reduced total dose, and improved efficiency in treatment. Another beneficial property of such systems is a possibility to control and manipulate drug release profile in accordance with specific requirements. Long-term sustained release formulations with the capacity of delivering drugs from days to months are very attractive option for conditions required regular administration of the drug, e.g., for management of chronic diseases or malnutrition-related conditions. For such cases, usually polymeric formulations based on biodegradable and biocompatible polymers are used. Among them, poly(D,L-lactide-co-glycolide) (PLGA) is a very popular choice. Unfortunately, formulations based on PLGA (when used alone or with additives) suffer from “burst release” of the drug during first few hours, in some cases up to 50% or more of the drug is released, which is not suitable for long-term drug delivery (above 24 h).

SUMMARY

Accordingly, in one aspect, the present disclosure provides compositions for sustained release of an active agent. In an aspect, the composition comprises an active agent, PLGA and an additive.

In yet another aspect, the present disclosure provides a long-term sustained release composition comprising an active agent, PLGA, and an additive.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1 illustrates microscope images of Iron (II) sulphate nanoparticles (IS NPs) (A, Stereo Zoom Microscope), and IS NPs containing PLGA-PEG-3 (70:30) film obtained using a) compound microscope (B) and b) stereo zoom microscope (C, D). Figure 2 illustrates IS NPs containing PLGA-PEG-3 (70:30) film on Petri dish.

Figure 3 illustrates release profiles of IS (cumulative release) in water from polymeric films of different compositions, insert shows daily release of IS from polymeric composition PLGA-PEG-3.

Figure 4 illustrates release profiles of various drugs in water from PLGA-PEG-2 and PLGA-PEG-3 films.

DETAILED DESCRIPTION

Before the present invention is described in greater detail, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

Certain ranges are presented herein with numerical values being preceded by the term "about." The term "about" is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described. All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.

It is noted that, as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only" and the like in connection with the recitation of claim elements, or use of a "negative" limitation.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention.

For convenience, certain terms used in the specification, examples, and appended claims are collected in this section.

As used herein, the term 'compound(s)' comprises the compounds disclosed in the present invention.

As used herein, the term "comprises" or "comprising" is generally used in the sense of include, that is to say permitting the presence of one or more features or components.

The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and/or animals without excessive toxicity, irritation, allergic response or other problem or complication, commensurate with a reasonable benefit/risk ratio.

"Pharmaceutically acceptable salt" refers to the salts of the compounds, that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Such salts include: salts derived from inorganic bases such as Li, Na, K, Ca, Mg, Fe, Cu, Zn, Al, Mn; salts of organic bases such as N,N'-diacetylethylenediamine, 2-dimethylaminoethanol, isopropylamine, morpholine, piperazine, piperidine, procaine, diethylamine, triethylamine, trimethylamine, tripropylamine, tromethamine, choline hydroxide, dicyclohexylamine, metformin, benzylamine, phenylethylamine, dialkylamine, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, pyrimidine, spermidine, and the like; chiral bases like alkylphenylamine, glycinol, phenyl glycinol and the like, salts of natural amino acids such as glycine, alanine, valine, leucine, isoleucine, lysine, arginine, serine, threonine, phenylalanine; unnatural amino acids such as D-isomers or substituted amino acids; salts of acidic amino acids such as aspartic acid, glutamic acid; guanidine, substituted guanidine wherein the substituents are selected from nitro, amino, alkyl, alkenyl, alkynyl, ammonium or substituted ammonium salts. Salts may include acid addition salts where appropriate which are sulphates, nitrates, phosphates, perchlorates, borates, hydrohalides, acetates, tartrates, maleates, citrates, succinates, methanesulfonates, benzoates, salicylates, hydroxynaphthoates, benzenesulfonates, ascorbates, and the likes thereof.

"Pharmaceutically acceptable solvates" may be hydrates or comprising other solvents of crystallization such as alcohols.

The term "stereoisomer" or "stereoisomers" refers to any enantiomers, diastereomers or geometrical isomers of the compounds as described herein, wherever they are chiral or when they bear one or more double bond. When the compounds are chiral, they can exist in racemic or in optically active form. It should be understood that the invention encompasses all stereochemical isomeric forms, including diastereomeric, enantiomeric and epimeric forms, as well as -isomers and /-isomers and mixtures thereof. Individual stereoisomers of compounds can be prepared synthetically from commercially available starting materials which contain chiral centers or by preparation of mixtures of enantiomeric products followed by separation such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, direct separation of enantiomers on chiral chromatographic columns, or any other appropriate method known in the art. Starting compounds of particular stereochemistry are either commercially available or can be made and resolved by techniques known in the art. Additionally, the compounds of the present invention may exist as geometric isomers. The present invention includes all cis, trans, syn, anti, entgegen (E) and zusammen (Z) isomers as well as the appropriate mixtures thereof.

The term "treat", "treating" or "treatment" is used herein to denote treating the disease, disorder, or condition, or ameliorating, alleviating, reducing, or suppressing symptoms of the disease, or slowing or stopping the progress of the disease.

As used herein, the term "transdermal" refers generally to application, administration, or delivery of a drug by means of direct contact with skin or mucosa. Such application, administration or delivery is also known as dermal, percutaneous, transmucosal and buccal. As used herein, “dermal” includes skin and mucosa, which includes buccal, nasal, oral, rectal, and vaginal mucosa. The term "transdermal delivery" refers to drug delivery across the skin, usually accomplished without breaking the skin.

As used herein, “transdermal drug delivery system” refers to a system (e.g., a device) comprising a composition that releases drug upon application to the skin (or any other surface noted above). A transdermal drug delivery system may comprise a drug-containing composition, and, optionally, a backing layer and/or a release liner layer. Many such systems are known in the art and commercially available, such as transdermal drug delivery patches.

The terms, "individual," "patient," or "subject" are used interchangeably herein and include any mammal, including animals, for example, primates, for example, humans, and other animals, for example, dogs, cats, swine, cattle, sheep, rodents, and horses. The compositions disclosed herein can be administered to a mammal, such as a human, but can also be other mammals, for example, an animal in need of veterinary treatment, for example, domestic animals (for example, dogs, cats, and the like), zoo and wild animals, farm animals (for example, cows, sheep, pigs, horses, and the like) and laboratory animals (for example, rats, mice, guinea pigs, and the like). The subject may be in need of treatment by delivery of a therapeutic agent, for example, transcutaneous delivery of a vaccine or transdermal delivery of a drug.

Each embodiment is provided by way of explanation of the invention and not by way of limitation of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made to the compounds, compositions and methods described herein without departing from the scope or spirit of the invention. For instance, features illustrated or described as part of one embodiment can be applied to another embodiment to yield a still further embodiment. Thus, it is intended that the present invention includes such modifications and variations and their equivalents. Other objects, features, and aspects of the present invention are disclosed in or are obvious from, the following detailed description. It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only and is not to be construed as limiting the broader aspects of the present invention.

In an embodiment, the present disclosure provides a composition for sustained release of an active agent. The composition comprises an active agent, PLGA and an additive.

The term “active agent” refers to any substance, a compound, a molecule, a drug, composition of matter or any combination thereof that provides some pharmacologic effect or beneficial effect. In certain embodiments, the active agent includes, but are not limited to, vitamins, nutrients, drugs, foods, food supplements, and other beneficial agents. The active agent may present in the form of a free base, salt, hydrate or complex. In certain embodiments, the active agent may present in the form of a free base. In some instances, the active agent may present in the form of a salt.

Examples of vitamins include, but are not limited to, vitamin A, vitamin Bl, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, vitamin B12, vitamin C, vitamin D, vitamin E, and vitamin K.

Examples of nutrients include, but are not limited to, minerals and electrolytes in its elemental form or in form of salt or complex, such as iron, manganese, copper, zinc, iodine, fluoride, selenium, folate, magnesium, phosphorus, molybdenum, sodium, and potassium.

Examples of drugs that may be used in the composition as described herein include, but are not limited to, drugs for management of chronic, incurable or other diseases required prolonged treatment, such as allergies (e.g. antihistamines, corticosteroids), alzheimer's disease (e.g., tacrine, rivastigmine, galantamine, donepezil, memantine, etc.), arthritis and chronic pains (acetaminophen, ibuprofen, naproxen sodium, celecoxib, amitriptyline, nortriptyline, opioids, etc.), Parkinson's disease (levodopa, COMT inhibitors, Dopamine agonists, MAO-B inhibitors, etc.), depression, anxiety or panic disorder (Imipramine), hypercholesterolemia (Fenofibrate), psychiatric conditions (Haloperidol), inflammation (Nimesulide) or rare disease, such as Duchenne muscular dystrophy (MDM, Corticosteroids, Ataluren, arbekacin, aminophylline). The drug can be any pharmaceutically acceptable salt form of a basic, acidic, or zwitterionic drug that meets these criteria. In certain embodiments, the drug may be in any pharmaceutically acceptable form. The term “pharmaceutically acceptable form" means any pharmaceutically acceptable derivative or variation, including salt forms, stereoisomers, stereoisomer mixtures, enantiomers, solvates, hydrates, prodmgs. polymorphs, isomorphs, and pseudomorphs. Examples of salt forms for basic drugs include, but are not limited to, acetate, citrate, chloride, bromide, iodide, mesylate, sulfate, tartrate phosphate, maleate, and lactate. Examples of salt forms for acidic drugs include the sodium, potassium, calcium, lithium, aluminium, zinc, magnesium, choline, meglumine, benzathine, procaine, diethanolamine, and the like. In some examples, iron sulphate nanoparticles (IS NPs) are used as drug.

In certain embodiments, the drug may be in the form of drug particles having small or reduced particle size, nanoparticles of drug, or amorphous form of the drug. In some instances, the drug may be in the form of nanoparticles. The term “nanoparticle” refers to particles having a particle size of nanometers. In certain embodiments, the nanoparticle may have a particle size of about 1-1000 nm. In some instances, the nanoparticle may have a particle size of about 1-500 nm, about 1-250 nm, about 1-100 nm, or about 1-50 nm. The nanoparticles of the drug can be prepared using any method known in the art. For example, in one method, the preparation of nanoparticles of the hydrophilic drug comprises of dissolution of the drug (5 mg) in an aqueous phase consisting of a solvent (0.3 ml of distilled water) and a co-solvent (0.6 ml of methanol). Polymer (25 mg of PLGA) is dissolved in an organic phase consisting of a non-solvent (4 ml of chloroform) and the organic phase is added drop wise to aqueous phase under stirring. The above mixture is added drop wise to 10 ml of distilled water containing 0.5% w/v of Pluronic F-68. Organic solvent is removed by stirring overnight. Nanoparticles are recovered by centrifugation for 30 min at 25,000 rpm, washed two times with distilled water to remove unentrapped drug and lyophilized for 24 h to yield freeze-dried nanoparticles.

In another method, the preparation of nanoparticles of the hydrophobic drug comprises of the polymer of choice, e. g. poly (Methacyclic acid-co-methyl-methyacrylate) polymer (100 mg) mixed with 10 mg of the drug and dissolved in 10 ml of organic solvent (e. g. dimethyl sulphoxide). The prepared organic phase is transferred into 500 ml beaker containing 100 mg of poloxamer 188 in 20 ml of distilled water under mechanical stirring for lh. Drug-polymeric nanoparticles are recovered by centrifugation for 30 min at 25,000 rpm, washed two times with distilled water to remove unentrapped drug and lyophilized for 24 h to yield freeze-dried nanoparticles. In certain embodiments, the active agent may present in an amount from about 10% to about 50% or from about 20% to about 50% by weight of the composition. In some instances, the active agent may present in an amount from about 20% to about 40% by weight of the composition such as about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, or about 39% by weight of the composition. In other instances, the active agent may present in an amount from about 10% to about 30% or from about 10% to about 20% by weight of the composition.

PLGA used in the composition may present in an amount from about 20% to about 80% by weight of the composition. In certain embodiments, the PLGA may present in an amount from about 20% to about 60% or from about 20% to about 40% or from about 20% to about 30% by weight of the composition. In certain embodiments, the molecular weight of the PLGA is from 05 kDa to 200 kDa. In some instances, the molecular weight of the PLGA is 60 kDa.

PLGA is a copolymer of poly lactic acid (PLA) and poly glycolic acid (PGA). The PLA and PGA may present in any ratio. In certain embodiments, polymer ratio of lactic acid and glycolic acid in the PLGA is from about 30:70 to 70:30. In some instances, the polymer ratio of lactic acid and glycolic acid in the PLGA is 50:50. In certain embodiments, the content of glycolc acid unit is higher than the lactic acid unit. In further embodiments, the free carboxylic acids of the PLGA may present in the form of esters.

The composition as described herein further comprises one or more additives. The additives may be added to increase mechanical strength or stability towards humidity (in the fabrication of microneedles), and to control drug release from the polymeric composition. In certain embodiments, the additive may present in an amount from about 2% to about 45% or from about 5% to about 30% or from about 5% to about 20% by weight of the composition. In certain embodiments, the additive is selected from a group comprising polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-hydroxypropyl methacrylamide) (PHPMA), polysiloxanes, polycaprolactone (PCL) hyaluronic acid, chitosan (CS), carboxymethylcellulose sodium, hydroxymethyl cellulose, polyethylene oxide, polyvinyl- 107, molidones and natural gums. In some instances, the additive is PEG or PVA.

PEG of different molecular weight may be used in the present disclosure. In certain embodiments, the PEG is selected from a group comprising PEG 2000, PEG 6000, PEG 10000 and PEG 20000. In some instances, the PEG is PEG 2000. In the composition, the PLGA and one or more additives may be present at any ratio. In certain embodiments, the ratio of PLGA to one or more additives is from about 1:100 to about 100:1. In some instances, the ratio of PLGA to additive is from about 1:50 to about 50:1 or from about 1:20 to about 20:1 or from about 1:10 to about 10:1 or from about 1:5 to about 5:1 or from about 1:4 to about 4:1 or from about 1:3 to about 3:1 or from about 1:2.5 to about 2.5:1 or from about 1:2 to about 2:1. In further instances, the ratio of PLGA to additive is from about 1:2.5 to about 2.5:1. In yet another instances, the ratio of PLGA to one or more additives is about 1:1 or about 70:30.

In certain embodiments, the present disclosure provides a composition comprising: an active agent in an amount from about 10% to about 50% by weight of the composition;

PLGA in an amount from about 20% to about 80% by weight of the composition; and one or more additives, wherein the additive is present in an amount from about 2% to about 45% by weight of the composition.

In certain embodiments, the compositions described herein are provided for sustained release of an active agent. In certain embodiments, the compositions provided herein provide sustained release of an active agent for at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days or longer. In some embodiments, the compositions provided herein provide sustained release of an active agent for at least 12 days. In further embodiments, the compositions provided herein provide sustained release of an active agent for at least 14 days.

The present disclosure also provides a drug delivery system comprising a composition as described herein. The drug delivery system may be useful for sustained release of the drug. The sustained release of the drug may be up to 14 days or more. In some instances, the sustained release of the drug is up to 14 days. Such drug delivery system may be in the form of depot, transdermal patches, or microneedles.

The compositions described herein may be administered alone or in combination with one or more pharmaceutically or nutraceutically acceptable carriers, diluents or excipients. “Pharmaceutically or nutraceutically acceptable carriers, diluents or excipients” include any adjuvant, preservative, stabilizer, emulsifier wetting agent, carrier, sweetening agent, suspending agent, isotonic agent, flavor enhancer, excipient, glidant, dye/colorant, dispersing agent, diluent, surfactant, or solvent, which has been approved by the United States Food and Drug Administration (USFDA) as being acceptable for use in humans or animals.

Suitable pharmaceutically or nutraceutically acceptable carriers, diluents, or excipients are selected based on the intended form of administration, and consistent with conventional pharmaceutical or nutraceutical practices. The carriers, diluents or excipients or may be employed to provide an additive, synergistically effective or therapeutically effective amount of the active agents. Suitable pharmaceutical carriers, diluents, excipients or vehicles are known in the art, e.g., as described in Remington's Pharmaceutical Sciences (1990) 18th ed.

The compositions described herein may be administered by known routes of administration, such as, oral, parenteral, intravenous, intra-arterial, topical, intramuscular, intracranial, intraorbital, cutaneous, subcutaneous, ophthalmic, intraventricular, intravitreal, intraspinal, intracapsular, intraperitoneal, intranasal, intracisternal, central nervous system (CNS) administration, and aerosol.

The dosage administered will vary depending upon various factors such as the activity of the specific active agent employed; the metabolic stability and length of action of the active agent; the age, sex, body weight, and health of the host or patient; the mode and time of administration; the rate of excretion; and the severity of the particular disorder or condition, etc.

In certain embodiments, the compositions as described herein may be useful for sustained release of one or more active agents.

The present disclosure also includes the use of the compositions described herein in the manufacture of a medicament.

In certain embodiments, the compositions as described herein may minimize or eliminate initial burst release of the drug. In some instances, the compositions as described herein may deliver equal amount of the drug daily thereby reducing toxicity of the drug and improving efficiency in the treatment of a subject.

The present disclosure further includes a method of treating a disease or condition, comprising administering the composition as described herein to a subject suffering from the disease or condition. In certain embodiments, the disease or condition is selected from a group comprising depression, anxiety, panic disorder, hypercholesterolemia, psychiatric conditions, inflammation, chronic, incurable diseases, such as allergies, alzheimer's disease, arthritis and chronic pain, and Parkinson's disease.

The present disclosure now being generally described, it will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain aspects and embodiments of the present disclosure, and are not intended to limit the present disclosure in any way.

A dissolving polymeric composition with improved long-term sustained drug release up to 14 days is developed and tested using iron sulphate nanoparticles (IS NPs) as an example drug. The study of the drug release in vitro from the composition showed linear release of IS during 14 days without initial burst effect.

EXAMPLES

EXAMPLE 1: PREPARATION OF IRON SULFATE NANOPARTICLES (IS NPs)

Iron (II) sulfate (IS, 25 mg) was dissolved in nano-pure water (18 mL) to form 5 mM solution. This IS aqueous solution was added dropwise to acetonitrile (ACN, 180 mL) under vigorous stirring. Precipitated IS NPs were collected and washed with ACN and dried. Figure 1A displays microscope images of IS NPs obtained using Stereo Zoom Microscope.

EXAMPLE 2: PREPARATION OF PLGA FILM CONTAINING “IS NPs”

PLGA (polymer ratio of lactic acid and glycolic acid is 50:50, molecular weight is 60 kDa, 45.9 mg) and additives (5-20%) were dissolved in ACN to form 10% w/v polymer solution.

A specific amount of IS NPs (Table 1) were added to PLGA solution and sonicated for 20-30 min to ensure equal dispersion of NPs in PLGA. The resulting final mixture was drop casted on a clean surface of the Petri dish and allowed dry. A photograph of the IS loaded PLGA film (Figures 1-2) obtained using compound microscope (Leica DM E Microscope, USA) and stereo zoom microscope (Zeiss stereo discovery v8, Germany). Images display equal distribution of the NPs over the PLGA film.

Table 1: Composition of IS NPs-containing PLGA films

EXAMPLE 3: PREPARATION OF PLGA-PEG FILM CONTAINING IS NPs PLGA (polymer ratio of lactic acid and glycolic acid is 50:50, molecular weight is 60 kDa) and PEG (PEG 2000, PEG 6000, PEG 10000 or PEG 20000) were co-dissolved at different ratios (Table 2) in ACN to form 10% w/v polymer solution. A specific amount of IS NPs was added to the solution and sonicated for 20-30 min to ensure equal dispersion of NPs in PLGA. The resulting final mixture was drop casted on a clean surface of the Petri dish and allowed dry.

EXAMPLE 4: PREPARATION OF PLGA-PEG FILM CONTAINING DRUG(S)

PLGA (polymer ratio of lactic acid and glycolic acid is 50:50, molecular weight is 60 kDa) and PEG (PEG 2000 or PEG 10000) were co-dissolved at selected ratio (the same as in example PLGA-PEG-3, Table 2) in ACN to form 10% w/v polymer solution. Then drug (for example, Imipramine, Fenofibrate, Haloperidol or Nimesulide was used in this example) was added to the solution (13.8 mg) and sonicated for 30 min to ensure equal dispersion of the drug in polymeric composition. The resulting final mixture was drop casted on a clean surface of the Petri dish and allowed dry. Table 2: Composition of IS NPs-containing PLGA-PEG films

EXAMPLE 5: IS RELEASE FROM PLGA AND PLGA-PEG FILMS

The release of IS from PLGA films was measured in nano-pure water with or without iron detection kit. The IS NPs loaded polymeric films were immersed in tightly closed falcon tubes filled with 3.5 mL of water. The samples were stirred continuously at 180 rpm maintained at 37 °C, at last day the sample was sonicated for 1 h in ultrasonic bath to ensure complete release of whole loaded amount of IS. At particular time intervals, the samples were measured by a UV spectrophotometer at 260 nm. When iron estimation kit was used, the sample (250 uL) was taken at required time points, 4 uL of chromophore from iron estimation kit was added and immediately diluted with 3.25 mL of water, incubated for 30 min and absorbance was measured at 508 nm. At last day, the absorbance was defined as 100% of IS release. Every experiment was repeated at least thrice, and an average value was calculated using calibration curve obtained using known amounts of IS. The examples of the same are presented in the tables below. The IS released profiles from the films of various compositions are shown in Figure 3. Table 3: IS release profile from PLGA and PLGA-PEG films at various time points

Table 3A

Table 3B

Table 3C

Table 3D

Table 3E

Table 3F

Table 3G

Table 3H

EXAMPLE 6: DRUG RELEASE FROM PLGA-PEG FILMS The release of drug from PLGA-PEG films was measured in nano-pure water using UV absorption method. The drug loaded polymeric films were immersed in tightly closed falcon tubes filled with 3.5 mL of water. The samples were stirred continuously at 180 rpm maintained at 37 °C, at last day the sample was sonicated for 1 h in ultrasonic bath to ensure complete release of whole loaded amount of drug. At particular time intervals, the samples were measured by a UV spectrophotometer. At last day, the absorbance was defined as 100% of drug release. Every experiment was repeated at least thrice, and an average value was calculated using calibration curve obtained using known amounts of drug. The examples of the same are presented in the table 4 below. The drug released profiles from the films are shown in Figure 4. Table 4: Drug release profile from PLGA-PEG-2 and PLGA-PEG-3 films at various time points

Table 4A

Table 4B

Claims

THE CLAIMS:

1. A composition comprising an active agent, poly(lactide-co-glycolide) (PLGA), and one or more additives; wherein the composition provides sustained release of the active agent.

2. The composition as claimed in claim 1, wherein the composition comprises: active agent in an amount from about 10% to about 50% by weight of the composition;

PLGA in an amount from about 20% to about 80% by weight of the composition; and one or more additives in an amount from about 2% to about 45% by weight of the composition.

3. The composition as claimed in claim 1 or claim 2, wherein ratio of PLGA to one or more additives is from about 1:100 to about 100:1.

4. The composition as claimed in any of the claims 1 to 3, wherein ratio of PLGA to one or more additives is about 70:30.

5. The composition as claimed in any of the claims 1 to 4, wherein polymer ratio of lactic acid and glycolic acid in the PLGA is from about 30:70 to 70:30.

6. The composition as claimed in any of the claims 1 to 5, wherein polymer ratio of lactic acid and glycolic acid in the PLGA is about 50:50.

7. The composition as claimed in any of the claims 1 to 6, wherein the active agent includes vitamins, nutrients, drugs, foods, and food supplements.

8. The composition as claimed in any of the claims 1 to 7, wherein one or more additives are selected from a group comprising polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-hydroxypropyl methacrylamide) (PHPMA), polysiloxanes, polycaprolactone (PCL) hyaluronic acid, chitosan (CS), carboxymethylcellulose sodium, hydroxymethyl cellulose, polyethylene oxide, polyvinyl- 107, molidones and natural gums.

9. The composition as claimed in any of the claims 1 to 8, wherein one or more additives is PEG or PVA.

10. The composition as claimed in any of the claims 1 to 9, wherein one or more additives is PEG.

11. The composition as claimed in any of the claims 1 to 10, wherein the composition further comprises a pharmaceutically or nutraceutically acceptable carrier, diluent, or excipient.