HYDROTALCITE AS A POTENTIAL DRUG DELIVERY VEHICLE FOR ASPIRIN 1
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Mukesh Sharma , Manish Dixit , Atindra Shukla , Manish Mishra , D. O. Shah , Tejal Soni , B. N. Suhagia 1 Shah-Schulman Center for Surface Science & Nanotechnology, Dharmsinh Desai University, Nadiad - 387001 2 Faculty of Pharmacy, Dharmsinh Desai University, Nadiad - 387001 Email: Sharma.mukesh62@gmail.com
ABSTRACT Synthesized layered double hydroxides, hydrotalcites (HTlc) were used as drug carriers for NSAIDs. Salicylic acid derivatives form one of the most common classes of NSAIDs. Aspirin, an acidic drug is slightly soluble in water, short half life and increase the risk of gastrointestinal ulcer as well as stomach bleeding. In the present study we chose aspirin as a drug candidate which possesses analgesic and anti-platelet properties and widely used being prescribed to heart patients ( to prevent heart at tacks, strokes & blood clot formation after post surgery). “Mg6Al2 (CO3) (OH)16 . 4H2O” of hydrotalcite contains exchangeable anions. By anion exchange process HT intercalate aspirin in to its layers. Our aim is to provide stability, solubility, and reduced of gastric adverse drug effects as well as its controlled / sustained release of the drug. Drug release of the intercalation compound was performed in vitro in different simulated intestinal pH fluid. Results from the intercalated drug process show that hydrotalcite is able to intercalate aspirin with a simple procedure and with a good drug loading capacity (40-55%). We have explored several conditions to load the drug into HT layers in order to optimize the drug loading. The kinetics analysis shows the importance of the diffusion through the particle in controlling the drug release rate. The obtained release shows that hydrotalcite may be used to prepare modified release formulations.
CHARACTERIZATION OF HTLc-ASPIRIN
INTRODUCTION
Aspirin (acetyl salicylic acid) is a salicylic acid derivatives and is one of the most popular and commonly used drugs. Hydrotalcite (HTlc), also known as “anionic clays” or “layered double hydroxides”constitute a large family of materials “Mg6Al2 (CO3) (OH)16 . 4H2O” . Hydrotalcite containing exchangeable anions like chloride, nitrate or hydroxides are the most suitable hosts for the uptake of API. Hydrotalcites are robust materials though, they tend to dissolve in presence of acid. They are known for their antacid properties.
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A s p ir in HTC F o r m u la t io n
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AIM OF PRESENT WORK
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Aspirin, a acidic substance was selected for the intercalation compounds of hydrotalcite like anionic clay with drug due to following properties: Short half life (15-60 min.) Slightly soluble in water Increase the risk of gastrointestinal ulcer as well as stomach bleeding. Instability in alkaline media
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Fig 2: Drug release profile for 24 hrs in Phosphate buffer pH 7.4
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Fig 3: FT-IR Spectra: Aspirin (pure), HTlc, & HTlc– Asp (Formulation)
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So the aim of present work was: Modify drug pharmacokinetics Maintain pharmacologically active drug levels for long periods, avoiding repeated administrations Increase the solubilization and bioavailability of drug To protect drug from degradation in different pH To reduce risk gastric adverse drug effects
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Aspirin is a good candidate for this study because of both its short half life and the presence, in the molecular formula, of a carboxylic group that allows aspirin intercalation between the layers of hydrotalcite via anionic exchange.
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MgAl-HTlc-CO3 MgAlOx
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CO2 free water
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Fig 4: Comparison between XRDP of Pure Hydrotalcite & its intercalation Compound with Aspirin
METHOD 1.Reconstruction method:
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Fig 5: DSC thermograms of Aspirin (pure), & HTlc-Aspirin
SUMMARY
MgAlOx Guest
MgAl-HTlc-OH
HTlc-Guest
Hydrotalcite ability to absorb the negatively charge pepsin onto its positively charged surface. Hydrotalcite is also capable of buffering pH of the stomach at about 4 for a long time. The double hydroxide of Mg and Al in the layer prevents the gastric mucosal damage caused by the salicylate anion. Thus, the anionic clay carrier shield the stomach wall without interfering with the NSAIDs action of the charge compensating salicylate anion. The in vitro dissolution studies show that the drug is released by a de-intercalation process due to the exchange of the drug with the ions present in the dissolution medium (phosphate buffer pH 7.4). Drug release profile shows controlled release of drug. (Fig 2) FT-IR spectrum of drug loaded HT shows characteristic ester peak at 1766 cm-1 which is Indicative of the presence of aspirin in HT interlayers. (Fig 3) Signals of crystalline drug Aspirin when entrapped in HT are suppressed, so that Change in XRD pattern is indicative of drug loading. (Fig 4)
CONCLUSIONS OPTIMIZATION OF DRUG LOADING
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Water : Iso Propyl Alcohol
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% Degradation of aspirin
Optimization of Drug loading Capacity parameters: 1.Different proportion of Water : Isopropyl alcohol 2.Reaction conditions 3.Time reaction ( 5 hrs) 4. Molar ratio of drug & HTlc
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The present study shows that Hydrotalcite could be a very potential candidate for Delivery and controlled release of drugs like aspirin. The interlayer region of this matrix can be considered a microvessel in which the drug may be stored and from which it is released by a deintercalation process due to the ions present in the small intestine. HTlc can intercalate aspirin, the intercalation procedure is simple, and the final product has a high drug load. Characterization techniques show the evidences of aspirin binding in the interlayers of Hydrotalcite. Being basic material HT reduces the adverse effects of the drug and releases drug at pH 7.4
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REFERENCES
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Fig 1: % degradation of Aspirin in different ratio of water : IPA ( after 48 hrs)
F. Cavani, F. Trifiro, A. Vaccani, “ Hydrotalcite type anionic clays: preparation, properties & applications”, Catalysis Today, 11 (1991) 173– 301. U. costantino, V. Ambrogi, M. Nocchetti, “Hydrotalcite like compounds: Versatile layered hosts of molecular anions with biological activity”, Microporous & Mesoporous Materials 107 (2008) 149-160. S. Miyata, “Anion-exchange properties of hydrotalcite like compounds”, Clays clay Minerals 31 (1983) 305-311.
This poster has been presented at Faculty of Pharmacy, Dharmsinh Desai University, Nadiad– 387001