Sodium alginate is a hygroscopic materials, although, stable at low humidities with cool conditions. Aqueous alternatives of sodium alginate are most steady at ph 4-10. Below ph3, alginic acidity is precipitated. Sodium alginate alternatives are susceptible to microbial spoilage during storage, which may effect on solution viscosity. Succeeding loss of viscosity scheduled to depolarization was noticed when sodium alginate was warmed above 70c. Arrangements formulated with sodium alginate for external use may be maintained with the addition of 0. 1% chlorocresol, chloroxylenol, or parabens in case the medium is acidic, benzoic acid may be used. Bulk materials should be stored in an airtight container in a very good and dry place.
Sodium alginate is incompatible with acridine derivatives, crystal violet, phenyl mercuric acetate and nitrate, heavy metals and ethanol in concentrations greater than 5%w/v. Low concentrations of electrolytes cause a rise in viscosity but high electrolyte concentrations leading to salting out of sodium alginate; salting out occurs if more than 4% of sodium chloride exists.
Sodium alginate is used in variety of oral and pharmaceutical formulations. In tablet formulations, sodium alginate can be utilized as both a binder and disintegrant. It has additionally been used as a diluents in capsule formulations and also been used in the planning of continual release oral formulations, since it can wait the dissolution of a drug from tablets, tablets and aqueous suspensions.
Recently, sodium alginate has been used for the aqueous microencapsulation of drugs on the other hand with the more conventional microencapsulation techniques which use organic solvent systems. It has also been used in the formation of nanoparticles.
The adhesive character of hydrogels ready from sodium alginate has been looked into and the drug release from oral mucosal adhesive tablets based in sodium alginate has been reported. Hydrogel systems formulated with alginates are also investigated for delivery of protein and peptides.
Therapeutically sodium alginate has been found in the blend with an h2 receptor antagonist in the management of gastroesophageal reflux so that as a haemostatic agent in surgical dressings. Alginate dressings, used to treat exuding wounds often contain significant amounts of sodium alginate as this improves the gelling properties. Sodium alginate is also found in cosmetics and foods at concentrations given in stand 4
Safety
Sodium alginate is trusted in cosmetics, food products, and pharmaceutical formulations, such as topical ointment products, including wound dressings. It is generally seen as a nontoxic and non-irritant materials, although excessive dental consumption may be dangerous. The WHO hasn't specified a satisfactory daily intake for alginic acid and alginate salts as the levels used in foods do not signify a risk to health.
Handling safety measures.
Sodium alginate may be irritant to eye or the respiratory system if inhaled as dust;eye cover, gloves, dirt respirator are needed while controlling. Sodium alginate should be dealt with in a well ventilated environment.
Related substances
The various substances related to sodium alginate include alginic acid, potassium alginate, calcium alginate, propylene glycol alginate.
CHITOSAN
Chitosan is a derivative of chitin and it is a unique polysaccharide and hydrophilic polymer.
Non Proprietary Names
BP: Chitosan hydrochloride
Ph Eur : Chitosan hydrochloridum
Chemistry
Preparation
The rule derivative of chitin, namely Chitosan (C6H11O4N)n is a unique polysaccharide and hydrophilic polymer which is extracted from the chitin, a polysaccharide found in exoskeletons of crustaceans. it is processed by removing the shells from shellfish such as shrimp, lobusters and crabs. The shells are then ground into a pulverous powder. This powder is then deacetylated. This calls for boiling chitin in focused alkali (50%) for a number of hours. This can produce chitosan with a degree of acetylation between 20-30%, the most popular commercial form of Chitosan. In that chitosan, the acetyl groupings are uniformly distributed along the polymer chain. This is on the other hand with the Chitosan of similar degree of acetylation, but isolated from fungal cell wall surfaces in which the acetylresidues are grouped into clusters. Special substance treatments must obtain completely de-acetylated kinds of chitosan.
CHITIN
Functional category
It is used as a layer agent; disintegrant; film developing agent; mucoadhesive, tablet binder; viscosity increasing agent etc.
Chemical character
Chitosan is a cationic polyamine with a higher charge denseness at ph<6. 5 so adheres to negatively incurred surface and chelates steel ions. It really is a linear polyelectrolyte with reactive hydroxyl and amino organizations so designed for chemical response and salt formation. Chitosan is a linear polysaccharide made up of randomly sent out î²-(1-4)-linked d-glucosamine (deacetylated device;d) and n-acetyle-d-glucosamine(acetyl product;a). The perentage degree of deacetylation (%da) of chitin can be determined by nmr spectroscopy, and the %da in commercial chitosan is at the number 60-100%. The viscosity of an chitosan solution mainly depend on the common molecular weight of the polymer, which may be determined by size exclusion chromatography combined with light scattering detection.
The amino group in chitosan has a pka value of around 6. 5, thus chitosan is favorably incurred and soluble in acidic to natural solution with a charge density rely upon ph and the %da. Numerous studies have exhibited that the salt form, molecular weight, and degree of deacetylation as well as ph at which chitosan is employed all impact how this polymer is employed in pharmaceutical program. Chitosan is incompatible with strong oxidising agent.
Typical properties
Chitosan is a cationic polyamine with a high charge denseness at ph<6. 5. It really is linear poly electrolyte with reactive hydroxyl and amino groups. The properties of chitosan relate to its poly electrolyte and polymeric carbohydrate character. The occurrence of a number of amino groupings allows chitosan to behave chemically with anionic systems, which results in alteration of physicochemical characteristics of such mixtures.
Acidity / alkalinity
pH=4-6(1%w/v aqueous solution)
Density
1. 35-1. 49g/cm3
Particle size distribution
<30m
Stability and safe-keeping conditions
Chitosan is a stable material at room temp though it is hygroscopic after drying. Chitosan should be stored in a tigjtly sealed container in a great and dry place.
Incompatibilities
Chitosan is incompatible with strong oxidizing real estate agents.
Safety
Chitosan is being investigated extensively for use as an excipient in oral and other pharmaceutical formulations. Additionally it is used in makeup products. chitosan is generally thought to be biodegradable, nontoxic and non irritant materials. it is biocompatible with both healthy and infected skin.
Applications
Chitosan is available useful in many areas like sustained medication delivery, components of mucoadhesive dosage forms, rapid release medication dosage forms, improved upon peptide delivery, colonic medicine delivery systems and use for gene delivery. Chitosan is processed into several pharmaceutical varieties including gels, beads, motion pictures, microspheres tablets and coatings for liposomes.
PROPRANOLOL HYDROCHLORIDE
(β-adrenergic blocking realtors)
Adrenergic nonselective β-receptor antagonist. (antihypertensive, antianginal and antiarrhythmic. )
STRUCTURE
Chemical name (±)-1-isopropylamino-3-(1-naphthyloxy) propan-2-ol
hydrochloride
Molecular solution C16H21NO2. HCl
Molecular weight 295. 8
Description: A white natural powder, odourless and bitter in taste
Solubility: Soluble Soluble 1 in 2 of drinking water and ethanol
Slightly soluble in chloroform
I. PHARMACOLOGICAL ACTIONS
a. Cardiovascular-Propranolol diminishes cardiac outcome, heart rate, and make of contraction. These effects are useful in the treatment of angina.
b. Peripheral vasoconstriction-Blockade of β-receptors prevents β2-mediated vasodilation. The decrease in cardiac output leads to decreased blood circulation pressure.
c. Bronchoconstriction-Blocking β2 receptors in the lungs of prone patients causes contraction of the bronchiolar simple muscle. Î'-blockers are thus contradicted in patients with asthma.
d. increased Na+ retention-reduced blood circulation pressure causes a reduction in renal perfusion, leading to a rise in Na+ and plasma size. occasionally this compensatory response will elevate the BP. For these patients, β-blockers are often combined with a diuretic to avoid Na+ retention.
II. Restorative EFFECTS
a. Hypertension-propranolol lowers BP in hypertension by lowering cardiac outcome.
b. glaucoma-propranolo is effective in diminishing intraocular pressure in glaucoma.
c. migraine-propranolol is also effective in minimizing migraine episodes by blocking the catecholamine induced vasodilation in the brain vasculature.
d. angina pectoris-propranolol reduces the oxygen dependence on heart muscle and for that reason effective in lowering the torso pain in angina.
e. myocardial infarction-propranolol and other β-blockers have a defensive influence on the myocardium. thus, patient who've got one myocardial infarction seem to be protected against a second heart attack by prophylactic use of β-blockers.
III. ADVERSE EFFECTS
a. broncho constriction-when propranolol is implemented with an asthmatic patient, an instantaneous contraction of the bronchiolar simple muscle prevents air from entering the lungs. Therefore, propranolol must never be utilized in treating anybody with obstructive pulmonary disease.
b. arrhythmias-treatment with the β-blockers must never be ceased quickly because of the risk of precipitating cardiac arrhythmias.
c. disturbances in metabolism- β bloackade leads to decreased glycogenolysis and decreased glucagon secretion.
d. medication interaction-drugs that interfere with the metabolism of propranolol, such as cimetidine, furosemide and chlorpromazine may potentiate its antihypertensive effects. conversely those that stimulate is metabolism, such as barbiturates, phenytoin and rifampicin can mitigate its effects.
PHARMACOKINETICS
Propranolol is well assimilated after oral supervision but has low bioavailability due to high first forward metabolism in liver organ. it is highly bound to plasma proteins.
Metabolism of propranolol would depend on hepatic blood circulation.
DOSE
Oral - 10mg BD to 10mg QID (average 40-60mg/day)
I. V - 2-8mg injected over 10min with with constant monitoring. it isn't injected S. C or I. M because of irritant property.
MATERIALS
NAME FROM THE MATERIALS
NAME IN THE COMPANY
Propranolol hydrochloride
Sodium alginate AR
Hi-Media biosciences Ltd, Mumbai.
Calcium chloride AR
S. D Fine chemicals Ltd, Mumbai
Barium chloride AR
Qualigens Fine Chemicals Ltd, Mumbai
Chitosan AR
Fluca Biochemicals Ltd, Switzerland. (Viscosity 200-400 mPa. s)
Acetic acid
EQUIPMENTS USED
Name of equipment
Name of company
UV/Vis Spectrophotometer
JASCO V-530
IR Spectrophotometer
Jasco-FT-IR 8201 PC
Differential scanning calorimeter
DSC-60 (Shimadzu, Tokyo, Japan)
Optical Microscope and Level Micrometer
Erma. Japan
Scanning Electron Microscope
JSM 6400
x-ray diffractrometer
Bruker AXS D8
Dissolution apparatus
Electrolab TDT-08L, USP XXIV Type I Apparatus. Chennai
Remi Hi-speed motor
Universal motors. Mumbai
Digital balance
Denver Instruments
18002098899 simi
INTRODUCTION
MICROENCAPSULATION
A process in which very thin coatings of polymeric materials are deposited around contaminants of solids or droplets of water.
Different conditions for stable particle systems are used in medicine delivery included in this pellets, beads, microcapsules, microspheres, millispheres are few. The terminologies of all relevant multiparticulate systems are given here.
Pellets can be defined as "Small, free moving spherical particles produced by agglomeration of fine powders or granules of medicine substances and excipients using appropriate handling equipment. " How big is these contaminants rae usually between 0. 5 and 1. 5mm. sphericity and intra granular porosity will be the two important quality attributes of pellets. The conditions 'spherical granules' and 'beads' have been applied interchangeably to pellet system.
Microspheres are solids about spherical particles varying in proportions from 1 to 1000m. They are constructed of polymeric, waxy, or other protective materials, that are biodegradable synthetic polymers and revised natural products such as gums, proteins, waxes etc.
Microsphere: the enbtrapped compound is dispersed throughout the microsphere matrix.
Microcapsule: the entrapped material is completely ornamented by distinctive capsule wall membrane.
The similiarities between microsphers and microcapsules are obvious and illustrations of the contaminants are shown in Fig:
Encapsulation methods
Two major classes of encapsulation methods have evolved, viz chemical and physical. The high grade of encapsulation will involve polymerisation through the process of getting ready the microcapsules. examples of this category are usually known by the name of interfacial polymerisation or in situ polymerisation. The next type involves manipulated precipitation of an polymeric solution where in physical changes usually appear.
The precipitation and or gelation stated in stand cover many techniques. one of these isthe precipitation of drinking water soluble polymers such as gelatin with water miscible solvents such as isopropranol. other for example the precipitation of ethyl cellulose from cyclohexane agin by cooling, and gelation of sodium alginate with aqueous calcium mineral salt solutions. in all cases the target is to precipitate a performed polymer round the primary (sometimes a multi-particulate) to cause encapsulation.
Process
- Coating material
- Suspended medium
- Interfacial polymerization
- Water soluble and insoluble monomers
- Aqueous/organic and natural solvents
- Complex coacervation
- Water soluble polyelectrolyte
- Water
- Simple coacervation
- Hydrophobic polymers
- Organic solvents
- Thermal denaturation
- Proteins
- Organic solvents
- Salting out
- Water-soluble polymer
- Water
- Solvent evaporation
- Hydrophilic or hydrophobic polymer
- Organic or Water
- Hot melt
- Hydrophilic or hydrophobic polymer
- Aqueous/organic and natural solvents
- Solvent removal
- Hydrophilic or hydrophobic polymer
- Organic solvents
- Spray drying
- Hydrophilic or hydrophobic polymer
- Air, nitrogen
- Phase separation
- Hydrophilic or hydrophobic polymer
- Aqueous/organic solvents
POLYMER BASED Medication DELIVERY SYSTEM
There has been growing fascination with polymer structured bioadhesive drug delivery systems. one of the goals of such systems is to lengthen the house time of a medication carrier in the Gastro Digestive tract(GIT). The bioadhesive relationship can be of a covalent, electrostatic, hydrophobicor hydrogen connection character. ionic polymers are reported to become more adhesive than neutral polymers, and an increased charge thickness will also give better adhesion suggesting that the electrostatic interactions are of great importance. aside from the oesophagus, the entire GI tract including the stomach is covered with a continous level of insoluble mucus gel. The mucus gel mainly contains glycolproteins and because of the content of ester sulphate and sialic acidity categories, the mucus level has an overall strong net negative demand. The mucus layer has been considered as a possible site for bioadhesion and drug delivery by several groups.
Natural polymers
Recently, the utilization of natural polymers in the design of drug delivery formulation has received much attention because of their excellent biocompatibility, biodegradability, non toxicity and easy in availability.
Polymers as companies used in drug delivery system
The different types of polymers for prolonged release preparations receive below.
Biodegradable polymers
The biodegradable polymers comprised of monomers linked to one another through functional teams and have unpredictable linkages in the backbone. They can be biologically degraded or eroded by enzymes or produced by living skin cells.
Natural
Albumin, alginate, collagen, starch, chitosan, dextran, casein, gelatine, fibrinogen etc.
Synthetic
Polyalklyl-cyanoacrylate, poly ethyl cyano acrylate, poly proteins, poly amides, poly acryl amides etc.
Aliphatic polyesters
Poly(maleicacid), poly (glycolic acidity), poly(hydroxyl butyrate), poly (lactic acid solution), poly vinyl fabric alcohol(PVA) etc.
Non-biodegradable polymers
Poly ethylene vinyl acetate(EVA), poly ether urethane(PEU), cellulose acetate, poly vinyl fabric chloride(PVC), ethyl cellulose etc.
In recent years a lrge range of biodegradable polymers have been investigated for his or her potential use as medication delivery systems. included in this, sodium alginate and chitosan are very promising and have been extensively exploited in pharmaceutical industry for sustained medicine release. polysaccharides such as alginic acid, agar, chitin and chitosan have been used to agglomerate drugs for controlled drug delivery systems.
Chitosan is a anaturally developing polysaccharide comprosing of glucosamine and N-Acetyl glucosamine with unique poly cation characteristics. The polycationic mother nature of chitosan leads to a strong connections with negatively priced alginate. when alginate is lowered into chitosan solution, the electrostatic connection of carboxylic groups of alginate with the amino sets of chitosan brings about the formation of a membarane on the surface of sodium alginate and boosts the stability and medication content. This technique has been widely used in the preparation of alginate chitosan membaranes with a solid calcium-alginate gel core. There are plenty of features of the chitosan covering, such as the improvement of drug loading and bioadhesive property, as well as the prolonged drug release properties etc.
Alginate(ionic, hydrophilic polymer) is a negatively recharged polysachharide with high fee density and has been reported to be bioadhesive. among polyanionic polymers, alginate has been greatly studied and requested its opportunity to modulate the release according to the properties of its carboxyl groupings as well as its biodegradability and lack of its toxicity. alginate is a effortlessly derived anionic polysaccharide mainly from algae belonging to the family of phaeophyceae. Alginic acidity can be an algal polysaccharide and a types of poly carboxylic acid. alginate involves two sugars moieties β-D mannuronic acid solution and α-L guluronic acidity which exist either in blocks or arbitrary sequences and their relative proportions determines the biofunctional properties of alginc acidity. alginate is known to form complexes with divalent cations, such as Ca2+, Ba2+, and Sr2+ in aqueous solution. depending upon the composition of two sugars residues and sequential distribution within the substances, the complexes form either precipitates or hydrogels. guluronic acidity blocks are recognized to form a rigid buckled composition, the so called "egg field" array, in which chelating calcium ions are nestled in the aqueous environment of the purchased gel structure because of the spatial agreements of guluronic block oxygen atoms of carboxyl and hydroxyl groupings.
Alginate has been trusted as food additive, a tablet disintegrator or gelation agent, and the system of its gelation have been thoroughly looked into. when an aqueous solution of sodium alginate(SA) is added dropwise to an aqueous solution of calcium chloride, spherical alginate beads with regular shape and size are produced, since an insoluble calcium mineral alginate matrix is made by the cation exchange between sodium and calcium mineral ions. alginates are recognized to form reticulated structure when in touch with calcium mineral chloride ions which characteristic has been used to produce SR particulate systems for a number of drugs.
GEL Development (Standard MECHANISM)
A gel in traditional colloidal terminology, is thought as a system which owes its characteristic properties to a combination associated network of polymeric chains which form at the gel point. a great deal of research has been carried out lately to elucidate the nature of the crosslinks and determine the composition of alginate gels. alginate beads can prepare yourself by extruding a remedy of sodium alginate formulated with the desired medication or proteins, as droplets, into a divalent crosslinking solution such as Ca2+, Ba2+, and Sr2+. monovalent cations do not stimulate gelation while Ba2+, and Sr2+ ions produce better alginate gels than Ca2+. other divalent cations such as Pb2+, Cu2+, Disc2+, CO2+, Ni2+, Zn2+, Mn2+ will also cross hyperlink alginate gels but their use is limited due to their toxicity. The gelation and mix linking of the polymers are mainly attained by the exchange of divalent cations and stacking of the guluronic acids with the divalent cations, and the stacking of these guluronic groups to form the quality egg-box framework shown in fig
LARGE BEAD PREPARATION
In standard, beads greater than 1. 0mm in diameter which is often produced by using a syringe, with a needle or a pipette. sodium alginate solution which has the solubilised drug or health proteins is transferred dropwise into a softly agitated divalent cross linking solution. The diameter of the beads made is dependant on the size of the needle used and the viscosity of the alginate solution. a more substantial diameter needle and higher viscosity solutions will produce much larger diameter beads. The viscosity of SA can also impact the shape of the microbeads produced. The beads become more spherical as the awareness of SA increased. however, generally SA solutions of greater than 5% are difficult to get ready.
Since, gelation occurs within an aqueous environment, alginate is a promising material as a food additive, medication formulation and useful even for encapsulation of living cells to safeguard them from immune reactions. utilizing this stable complex development with divalent cations, alginate gels have been utilised for analysis of cells are believed to be the best system for the pulsatile release of biologically productive compounds.
Formulation of delivery devices for health proteins and peptide drugs under aqueous conditions are suitable to enough time undesirable loss of bioactivities which may occur when working with organic and natural solvents or heating during formulations. since relatively steady alginate gels can be developed in aqueous surroundings through chelation or complexation, which can be promising delivery of matrices for bioactive compounds.
It has been advised that the crosslinks were brought on either by ionic bridging of 2 carboxyl categories on adjacent polymer chains via calcium mineral ions or by chelation of solitary calcium mineral ions by hydroxyl and carboxyl groups on each of a pair of polymer chains. although these bonds may play a role in the gelation system that are not sufficiently energetically favourable to take into account the gelation of alginate. it has been shown on thebasis of fibre diffraction data and model-building calculations that the condition of both poly-mannuronic acid solution segments and the polygulutended, and these expanded ribbons can stack collectively in sheets. based on these data and the properties of gels it has been recommended that the cooperative relationship of either polymannuronic acidity sections or polyguluronic acidity segments get excited about the forming of the crosslinked network of polymer string.
This technique has shown attractive applications in several domains, including cell immobilisation, due to its minor operating conditions. as the encapsulation method is light, and done at room heat range in aqueous medium, several very sensitive drugs, proteins, living cells, enzymes, spermatozoa etc have been efficiently encapsulated through alginate beads.
The primary structure of alginate depends on the producing kinds and for the marine kinds, seasonal and geographical changes might result in variations in alginates extracted from the same varieties. The polymer is nown to create a physical gel by hydrogen bonding at low pH(acid gel)and by ionic relationships with polyvalent cations such as calcium mineral, the cation behaving as a mix linker between your polymer chains. The viscosity and major framework of polymer are important features determining it bloating and gelling properties.
At neutral pH, sodium alginate is soluble and hydrates to form viscous solutions, but below pH3, alginic acid, water swellable but insoluble, which is quickly formed. since the hydration characteristics of the polymer and the subsequent physical properties of the hydrated gel part may critically impact drug release.
When CA beads are treated with 0. 1M HCl, alginate gels hydrolysed to lessen molecular weight fractions of alginic acid solution. due to conversion of COO- groupings into unionised carboxylic categories, the electrostatic attraction between Ca2+ ions and COO- ions in the egg-box junction almost disappears. furthermore, there may occur in ion-exchange between H+ ion(existence in the exterior HCl solution) and free Ca2+ ions inside the beads. thus a lower life expectancy Ca2+ ions attentiveness within the beads results in a weaker Ca2+ mix connected beads when put in phosphate buffer at pH 6. 8. Therefore, the acid-treated beads are loosely crosslinked structure more soluble alginate as constituent. when such beads are put in the phosphate buffer pH6. 8, the beads swell at a faster rate but do not attain a higher water uptake value scheduled to loosely bound structure of the beads which is unable to retain massive amount water within the beads. additionally, there is opportunity of ion-exchange between H+ ions produced credited to ionisation of carboxylic organizations in the buffer at pH.
A group of scientists developed a method of enclosing feasible cells, tissues, and other labile natural substances in just a semipermeable membrane. initial in-vitro studies of several types of microencapsulated cells and tissues(redblood skin cells, sperm cells, hepatica skin cells, hepatocytes, pancreatic endocrine tissue, and islets) were described by them. essentially, the process consists of suspending the living cells or tissue in sodium alginate solution. The cell or tissue suspension system is extruded through a device producing micro-droplets which get into a calcium mineral chloride solution and form gelled microbeads with the skin cells or cells entrapped. These cell including gel microbeads are next cured with polysine which displaces the surface layer of calcium mineral ions and varieties a everlasting polysalt shell or membrane. finally, the interior calcium alginate is "liquefied", either in which to stay or even to cum out(depending on molecular weight and size of the starting alginate) of the capsule with a calcium mineral sequestrant such as buffered citrate solution.
Gohel et al. , prepared diclofenac sodium microspeheres by using sodium alginate as a polymer and CaCl2 as a combination linking agent. in this research stirring speed, awareness of crosslinking agent and heavy liquid paraffin were researched, on enough time necessary for 80% of drug dissolution. a statistical model with significant discussion terms was produced to predict t80 and medicine premiered by diffusion of anomalous type. The results of multiple regression research and F value figures discovered that, obtaining of managed drug release and microspheres were to be prepared using relatively lower stirring swiftness.
Literature reports suggest wide spread use of sodium alginate for attaining suffered release of drugs, targeting gastric mucosa and increasing the bioavailability of drugs because of sodium alginate's capacity to form a well balanced and bioadhesive gel with calcium mineral ions.
Alginate also has several unique properties which have empowered it to be utilized as a matrix for the entrapment or delivery of a number of protein, macromolecules and skin cells.
USES Of Alginate Beads
- A relatively inert aqueous environment within the matrix.
- A light room temperatures encapsulation process free from organic solvent
- A high gel porosity that allows for high diffusion rate of macromolecules
- The ability to regulate this porosity with simple finish procedures.
- Dissolution and biodegradation of the machine under normal physiological conditions.
Standard graph for propranolol hydrochloride
A stock solution of propranolol hydrochloride was prepared by dissolving 100mg of the drug in 100ml of the phosphate buffer of pH6. 8 to give 1mg/ml solution. ten millilitres of stock solution was diluted to 100ml using phosphate buffer f pH6. 8 to create 100g/ml working stock solution. from this working solution, dilutions were made with phosphate buffer of pH6. 8 to produce 10, 20, 30, 40 and 50 g/ml. The λ maximum of the drug was dependant on checking the dilutions between 400 and 200nm utilizing a Shimadzu 1400 UV visible spectrophotometer. As of this wavelength, the absorbances of all the other alternatives were measured against a bare. Standard curve between awareness and absorbance was plotted.
COMPATIBILITY STUDIES
One of the requirements for the selection of appropriate polymers or carriers for pharmaceutical formulation is its compatibility. Therefore in the present work a compatibility research was done by using Infra Red spectroscopy (IR) and Differential Scanning Calorimetry (DSC) to learn when there is any possible chemical substance connections between propranolol hydrochloride and the polymers.
DIFFERENTIAL SCANNING CALORIMETRY (DSC)
Differential Scanning calorimetric examination was used to characterize the thermal behaviour of the drug substances. It had been performed by using DSC-60(Shimadzu, Tokyo, Japan) calorimeter to study the thermal behavior of decided on formulations. The tool made up of calorimeter (DSC60), flow controller (FCL60), thermal analyzer (TA60) and working software(TA 60). The samples were heated up in hermetically sealed aluminium pans under nitrogen circulation (30ml/min)at a scanning rate of 5C/min from 24 + 1C to 300C. A clear aluminium pan, closed in the same way as the test was used as a guide.
SCANNING ELECTRON MICROSCOPY
Scanning electron microscopy is used to obtain the surface topographical characterization of beads. SEM photos of ready formulations were used with (Instrument JSM-6390)at different magnification which range from 30 to 5000x at room temp. The samples were attached to dual sided adhesive tape that has recently been secured on copper stubs. The acceleration voltage was taken care of at 20kv, with a secondary electron image (SEI) as a detector.
DRUG CONTENT ANALYSIS
DETERMINATION OF DRUG ENTRAPMENT EFFICIENCY
Fifty milligrams of medicine loaded alginate beads from each batch was placed in 100ml conical flask formulated with 50ml of phosphate buffer (pH6. 8). The beads were agitated on mechanised shaker every day and night, to promote the swelling and split up of the cross-linked structure. Then alternatives were filtered and the medication was quantified at 290nm spectrophotometrically after appropriate dilution with buffer. The entrapment efficiency (EE) was determined using the quoted empirical romance. Each conviction was performed in triplicate manner.
Entrapment Efficiency (%) = Actual medicine content (AC) Ã- 100
Theoretical drug content (TC)
AC - Real quantity of medicine present in the beads.
TC - 100% theoretical quantity of drug within the beads (genuine initial dose)
DRUG RELEASE STUDIES
IN VITRO DRUG RELEASE STUDIES
100mg of medicine packed alginate beads were examined for in vitro medicine release. The analysis was completed in the USP XXIV Type I apparatus using 900ml phosphate buffer (ph6. 8) solution and rotated at constant quickness (75rpm) and the temperatures of the medium was retained at 37±0. 5C for 8 hours. A muslin cloth was tied above the basket to avoid the slippage of beads from the basket. An aliquot of the sample (5ml) was occasionally withdrawn at the regular time intervals (0, 0. 5, 1, 2, 4, 6 & 8hrs) and the same volume was substituted with fresh dissolution medium. The test samples were filtered and analysed spectrophotometrically at 274nm after appropriate dilution with buffer. The analysis was performed in triplicate for each batch. The percentage medication released at different time intervals were determined. The in vitro medicine release profiles were obtained by plotting the percentage release vs. amount of time in hours.
