DEVELOPMENT AND EVALUATION OF FLOATING TABLETS OF CIPROFLOXACIN HCL - REVIEW OF LITERATURE

 

REVIEW OF LITERATURE

 

Literature Survey

S.Stithit, et al.²⁶ Developed and characterised buoyant theophylline microspheres. The microspheres were prepared by a modified emulsion-solvent evaporation method using a polymer mixture of cellulose acetate butyrate and eudragit RL100. The prepared microspheres characterised for size distribution, morphology, density, drug polymer content, buoyant capacity and drug release behaviour. They found that microspheres were spherical with relatively smooth surfaces with round hollow cavities. The microspheres remained floating for more than 24hr in pH 1.2 and 7.5 buffers. The dissolution profile of the floating microspheres showed near zero order kinetics and sustained release in both pH 1.2 and 7.5 buffers.

 

Naggar V.F, et al.²⁷ Prepared and evaluated ketoprofen microspheres by employing emulsion- solvent diffusion technique. Eudragit S100 with eudragit RL were used as a coating material to form the floating microparticles. They studied all floating  microparticles  for good flow properties, particle size analysis, floating ability and for release rate.

 

Bodmeier R, et al.²⁸ designed verapamil HCL floating microparticles by using solvent diffusion method. Microparticles prepared by using Eudragit RS, ethyl cellulose and polymethyl methacrylate as a polymers. They studied effect of various polymers and processing parameters on the internal and external particle morphology, drug loading, in vitro floating behaviour, in vitro release kinetics, particle size distribution and physical state of the incorporated drug.

Park H.J, et al.²⁹ Prepared Riboflavin alginate beads for floating drug delivery system. Floating beads were prepared from a sodium alginate solution containing CacO3 or NaHCO3 as gas generating agents. The effect of gas generating agent on bead size and floating properties were investigated. The in vitro release studies carried out in 500 ml of PBS media at 100 rpm.

 

Yansuri Sato, et al.³⁰ Reported In vitro evaluation of floating and drug releasing behaviour of hollow microspheres (microballoons) prepared by emulsion solvent diffusion method. Microballoons were prepared by utilizing enteric acrylic polymers co dissolved with a drug in a mixture of a dichloromethane and ethanol. The release characteristics of riboflavin drugs exhibiting distinct water solubilities entrapped within microballoons were investigated. They concluded that the buoyancy of the microballoons decreased with increase in drug release rate. The drug release profiles of microballoons proved a linear relationship by Higuchi plotting. In addition by incorporating polymers such as a hydroxypropylmethylcellulose within the shell of microballoons, the release rate of riboflavin could be controlled while maintaining high buoyancy.

 

Srivastva A.K, et al.³¹ Formulated and characterised floating microspheres of cimetidine by using solvent evaporation method. Microspheres were prepared by using HPMC and EC as a polymers. They reported that prepared microspheres exhibited prolonged drug release (~8hr) and remained buoyant for > 10 hr and concluded that the floating microspheres may proved to be potential candidate for any intragasric condition.

 

Sriamornsak P, et al.³² Studied use of pectin as a carrier for intragastric floating drug delivery containing carbonate salt beads. The CaPG beads containing carbonate salt, as a gas-forming agent, were prepared by dispersing carbonate salt in pectin solution and then extruding into either neutral or acidified solution of calcium chloride. They investigated the effect of selected factors, such as type of carbonates, percentage of carbonates, degree of methyl esterification (DE) of pectin, type of gelation medium, drug loading and drying method, on morphology, floating and release properties.

 

Patel A, et al.³³ Reported in vitro evaluation of controlled release of floating drug delivery system of metformin hydrochloride by Non-aqueous solvent evaporation method. Microspheres prepared by using ethyl cellulose as a polymers. They concluded that he drug release of microspheres (47%-48% after 8 hr), floating time is (>8 hr). They have a concluded that drug loaded floating microspheres are a suitable delivery system for metformin hydrochloride.

 

Kouchak M, et al.³⁴ Prepared and evaluated a microballoon delivery system for theophylline. They employed emulsion solvent diffuson method to preprare microspheres by incorporating ethycellulose as a polymers. They have investigated physical characteristics, shape, size, floating capability, drug loading and drug release of theophylline of microspheres. They concluded that mean geometric diameter of microspheres decreased as the stirring speed increased and the microballoons prepared at a higher rates released their drug content faster. Also, concluded that particle size and floating capability of microballoons could be adjusted by altering the stirring rate during microencapsulation.

 

Jain S. K, et al.³⁵ Evaluated a porous carrier-based floating orlisat micropsheres for gastric delivery. Eudragit was used as a polymer and microspheres were developed by solvent evaporation technique. They studied various formulation and process variables on the particle morphology, micromeritic properties, in vitro floating behaviour, percentage drug entrapment and in vitro drug release. They concluded that release pattern of orlisat in simulated gastric fluid from all floating microspheres followed Higuchi matrix model and Peppas-Korsmeyer model.

 

Malay KD, et al.³⁶ Developed and evaluated zidovudine encapsulated ethylcellulose microspheres prepared by water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion technique. They found that DSC thermograms confirmed the absence of any drug-polymer interaction. Scanning electron microscopy studies showed that the microspheres were spherical and porous in nature.

 

Pawar AP, et al.³⁷ Developed hollow/porous calcium pectinate beads for floating-pulsatile drug delivery. They investigated influence of formulation parameters based on some independent variables. i.e. drug loading , amount of pectin and concentration of sodium biocarbonate. The dependant variables are particle size and drug entrapment ratio. They concluded that buoyant beads provide a lag phase while showing gastroretention followed by a pulsatile drug release.

 

Stops F, et al.³⁸ Designed a floating dosage forms to prolong gastro retention with characterisation of calcium alginate beads. They investigated information about structure, floating ability and changes that occurred when the dosage form was placed in aqueous media and release characteristics.   

Tanwar YS, et al.³⁹ Developed and evaluated a floating microspheres of verapamil hydrochloride. The nature of polymer influenced the physical characteristics as well as floating behaviour of the microspheres. In vitro buoyancy and in vivo studies confirmed the excellent floating properties of cellulose acetate microspheres. The drug release was sufficiently sustained and non Fickian transport of the drug from floating microspheres was confirmed.

 

Li Sanming, et al.⁴⁰ Developed and evaluated a sustain release microspheres. Microspheres were prepared by the ionotropic gelation technique method with calcium carbonate being used as a gas-forming agent. Attempts were made to enhance the drug encapsulation efficiency and delay the drug release by adding chitosan into the gelation medium and by coating with eudragit. They found that drug encapsulation efficiency of microsphere coated with Eudragit RS could extend the drug release significantly. Microspheres were able to continuously float over the simulated gastric fluid for 24 h in vitro.

 

Basavaraj BV, et al.⁴¹ Reported hollow microspheres of diclofenac sodium. Microballoons of diclofenac sodium prepared with an acrylic polymer Eudragit S100 in different ratios by emulsion solvent diffusion method were optimized. The formulation MB-2, with drug polymer ratio(1:2) showed better physicochemical and micromeritic properties on comparison to original drug. It was noticed that the increase in polymer concentration decreased the drug release from the microballoons due to increased thickness of the outer shells.

 

Basavaraj BV, et al.⁴² Designed controlled drug delivery system of famotidine. Microspheres were prepared by emulsion solvent diffusion method by using Eudragit S-100 as a polymer.  They found that percentage of drug encapsulation and recovery was found to be 75%-80%. The buoyancy showed that they remain floated in the simulated gastric fluid for more than 12 h. In vitro dissolution profile showed prolonged release of drug from the formulation demonstrating non-Fickian diffusion of drug from the hollow microspheres.

 

Deshmukh PK, et al.⁴³ Studied floating drug delivery system prepared by emulsion gelation technique. Amoxicillin trihydrate and sodium alginate used as a core:coat material. They found that percentage buoyancy of formulation showed a good result. Microspheres formed were spherical in shape. Encapsulation efficiency was a 97.42%.

 

Barhate SD, et al.⁴⁴ Formulated and evaluated floating microspheres of ketorolac trometamol. The floating drug delivery system of ketorolac was prepared by emulsion solvent diffusion method by using ethyl cellulose, HPMC K4M, Eudragit R100, Eudragit S 100 polymers in various concentration.  Formulation were evaluated for percentage yield, particle size, entrapment efficiency, in vitro buoyancy and in vivo release studies.

 

Deepa MK, et al.⁴⁵ Developed floating microspheres of cefpodoxime proxetil in order to achieve an extended retention in the upper GIT. The microspheres were prepared by non-aqueous solvent evaporation method using polymers such as hydroxylpropylmethylcellulose and ethyl cellulose in different ratios. Microspheres were characterized by polymer compability by using FT-IR, the yield, particle size, buoyancy percentage, drug entrapment efficiency and in vivo drug release study.

Jain AK, et al.⁴⁶ Studied effect of biodegradable and synthetic polymer for gastric diseases by floating microspheres. The microspheres were prepared by the solvent evaporation method using polymers acrycoat S100 and chitosan. They observed the effects of natural biodegradable polymer chitosan and another acrycoat S 100 polymer on the size of microspheres, incorporation efficiency and in-vitro drug release. They have concluded that the prepared microspheres exhibited prolonged drug release more than 18 hr, incorporation efficiency was change due to increase concentration of poly vinyl alcohol solution.

 

Punitha K, et al.⁴⁷ Formulated and evaluated floating drug delivery system of a ranitidine hydrochloride. Floating microspheres prepared with HPMC 15 cps and Eudragit E‐100 in various ratios. They evaluated all formulations for FTIR, drug loading, % entrapment, particle size, SEM, buoyancy, dissolution study and the drug release kinetics.

 

Bharadwaj P, et al.⁴⁸ Prepared and evaluated floating microballoons of indomethacin as a model drug to increase its residence time in the stomach without the mucosa. The microballoons were prepared by the emulsion solvent diffusion technique using Eudragit RS100 and Eudragit S 100 as a polymer. The dissolution profile of indomethacin followed a Higuchi and Korsmeyer Peppas model. They concluded that changing the ratio of polymers indomethacin release can be controlled.

 

Md. Habibur Rahman, et al.⁴⁹ Designed and evaluated influence of HPMC K 100 and poloxamer 188 on release kinetics of curcumin in floating microspheres. The microspheres were prepared by solvent evaporation method and evaluated for the size of microspheres, drug incorporation efficiency, percentage yield, buoyancy percentage and in vitro drug release.

Drug release kinetics was evaluated using linera regression method. They concluded that influence of agitation speed showed minimum significance on drug release profile and curcumin microspheres could be used as a drug delivery system to improve absorption kinetics of curcumin.

 

Dhoka V, et al.⁵⁰ Formulated ethyl cellulose based floating microspheres of cefpodoxime proxetil. The microspheres were prepared by solvent evaporation technique and characterized for drug content, percent yield, particle size analysis and surface morphology.

 

Salunke P, et al.⁵¹ Formulated microcarriers of antidiabetic drug by using ionotropic gelation method by using HPMC K 4 M, ethyl cellulose as a polymer. The prepared microcarriers were evaluated for micromeritic properties. Percentage yield, drug loading, drug entrapment effiency, particle size and shape. Buoyancy and in vivo release studies. They studied formulations with different weight ratios of gas-forming agent and combination of polymer. They concluded that Ionotropic gelation method

can successfully used for preparation of antidiabetic drug using different polymer and gas forming agent.

 

Yadav A, et al.⁵² Developed and characterized floating microballoons of metformin prepared by emulsion solvent diffusion method. They found that preparation temperature determined the formation of cavity inside the microballoons and surface smoothness, floatability and drug release rate of the microballoons. They also studied correlation between the buoyancy of microballoons and their physical properties. They also determined drug loading efficiency.

 

Pandey M, et al.⁵³ Formulated and evaluated floating microspheres of famotidine. Floating microspheres were prepared by solvent evaporation (Oil-in-water emulsion) technique using hydroxylpropyl methylcellulose (HPMC) and Ethylcellulose (EC) as the rate controlling polymers. They performed studies on Particle size analysis, drug entrapment efficiency, surface topography, buoyancy percentage and release rate.

 

Senthilkumar SK, et al.⁵⁴ Formulated, characterized and evaluated floating microsphere containing rabeprazole sodium. The microspheres were prepared by the solvent evaporation method using different polymers like Hydroxy propyl methyl cellulose and Methyl cellulose. They studied the average diameter and surface morphology of the prepared microsphere by optical microscope and scanning electron microscopic methods respectively. They performed In vitro drug release studies and the drug release kinetics using linear regression method. They evaluated  microspheres for particle size, in vitro release, and buoyancy and incorporation efficiency.

 

Jiabi Zhu, et al.⁵⁵ Prepared and evaluated glyceryl monooleate-coated hollow bioadhesive microspheres for gastroretentive drug delivey using ethyl cellulose and eudragir EPO as a polymer by using emulsion solvent diffusion method. They concluded that preparation of microspheres was simple, reliable and inexpensive and prepared microspheres were smooth spherical in shape.

 

Masareddy RS, et al.⁵⁶ Formulated, evaluated and optimized Metformin Hcl loaded sodium alginate floating microspheres prepared by Ionotropic gelation technique with sodium bi-carbonate as gas forming agent with swellable polymers HPMC E50, ethyl cellulose and calcium chloride gelling agent. They evaluated microspheres for size analysis, drug loading, drug efficiency, buoyancy studies, SEM and in vivo release studies. They found that drug loading and drug entrapment effiency was found to be in acceptable range. All formulations possesssd good floating properties more than 12 hr. They concluded that spherical and free flowing microspheres of metformin hcl could be successfully prepared by ionotropic gelation technique with high entrapment efficiency and prolonged release characteristics.

 

Sangle s, et al.⁵⁷ Formulated and evaluated floating microspheres of felodipine by solvent evaporation method. Prepared microspheres were analysed for drug entrapment, bulk density, angle of repose, particle size and in vivo relese pattern. They concluded that prepared microspheres with solvent evaporation method was able to sustained release effectively.

 

Aphale S, et al.⁵⁸ Developed and Evaluated hollow microspheres  of clarithromycin as a gastroretentive  drug delivery system using eudragit polymers. Microspheres were prepared by emulsion solvent diffusion method. Eudragit S 100, RS 100, RL 100, L 100 and L 100 55 were used to prepare hollow microspheres. The microspheres were characterized for shape and surface morphology by scanning electron microscopy. They were evaluated for particle size, flow properties, bulk density, % drug entrapment efficiency, floating properties and in-vitro drug release.

                               

Pahwa R, et al.⁵⁹ Formulated and evaluated floating multipaticulate drug delivery system of glipizide. Floating microspheres were prepared by ionotropic gelation method using polymeric material such as chitosan. They have utilized D-optimal design to investigate the joint influence of two variables: drug to polymer ratio (X1) and concentration of effervescent agent (X2) on the drug entrapment efficiency, percentage buoyancy, and cumulative percentage drug release. They have evaluated Particle size and surface morphology of prepared microspheres by optical and scanning electron microscopy respectively.

Lian-Dong Hu, et al.⁶⁰ Optimized gastric floating microspheres of dextromethorphan hydrobromide using a Central Composite Design. These microspheres were prepared by emulsion-solvent diffusion technique using ethyl cellulose (as carrier polymer) with drug in a mixture of dichloromethane and ethyl acetate. The physico-chemical properties of microspheres such as floating ability, drug loading, entrapment efficiency and in vitro drug release were investigated.

 

Singh B, et al.⁶¹ Synthesized gastroretentive floating sterculia-alginate beads for use in antiulcer drug delivery by ionotropic gelation metod.   They design beads by simultaneously ionotropic gelation of alginate and sterculia gum by using CaCl2 as crosslinker. The beads thus formed have been characterized by scanning electron micrographs (SEM), electron dispersion X-ray analysis (EDAX), fourier transform infrared spectroscopy (FTIR) analysis. The swelling of beads has been carried out as a function of various reaction parameters and pH of the swelling media. In addition, they studied in vitro release of drug from drug loaded beads in different release media for the evaluation of the drug release mechanism and diffusion coefficients. They concluded that Release of drug from beads occurred through Ficknian type diffusion mechanism.

 

Shah SH , et al.⁶²  Reported stomach specific floating drug delivery system: a review It is known that differences in gastric physiology, such as, gastric pH, and motility exhibit both intra-as well as inter-subject variability demonstrating significant impact on gastric retention time and drug delivery behaviour. This triggered the attention towards formulation of stomach specific (gastro retentive) dosage forms. This dosage forms will be very much useful to deliver ‘narrow absorption window’ drugs. Several approaches are currently utilized in the prolongation of the GRT, including floating drug delivery systems (FDDS), swelling and expanding systems, polymeric bioadhesive systems, high-density systems, modified-shape systems and other delayed gastric emptying devices. In this review, current & recent developments of Stomach Specific FDDS are discussed.

 

Drug Profile

CIPROFLOXACIN HYDROCHLORIDE63

Chemical structure

 

Molecular formula                  :            C17H18FN3O3HCl•H2O

Molecular weight                    :           385.8

Chemical name                       :            1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)                                quinoline-3-carboxylic acid

Solubility                                    :           Soluble in ethanol and a buffered aqueous

                                                            solution with a pH of 2.3; solubility decreases

                                                            with increasing pH in the physiologic range.

Category                                :           Anti bacterial agent

Description                             :           A faintly yellowish to light yellow crystalline

pKa                                        :      6.8 and 6.1.

Pharmacology:

            Ciprofloxacin is a synthetic antibiotic of the fluoroquinolone drug class. It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of protein.

 

Mode of action:                    

            Ciprofloxacin is a broad-spectrum antibiotic active against both Gram-positive and Gram- negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, enzymes necessary to separate bacterial DNA, thereby inhibiting cell division. This mechanism can also affect mammalian cell replication. In particular, some congeners of this drug family (for example those that contain the C-8 fluorine) display high activity not only against bacterial topo isomerases but also against eukaryotic topoisomerases.

 

Pharmacokinetics:

            The effects of 200–400 mg of ciprofloxacin given intravenously are linear drug accumulation does not occur when administered at 12 hour intervals. Bioavailability is approximately  70-80%,  with  no  significant  first  pass effect. IV administration produces a similar serum levels as those achieved with administration of 500 mg administered orally. IV administration over 60 minutes given every 8 hours produces similar serum levels of the drug as 750 mg administered orally every 12 hours. Biotransformation is hepatic. The elimination half life is 4 hours.

Adverse reactions:

            The serious adverse effects that may occur as a result of ciprofloxacin therapy include irreversible peripheral neuropathy spontaneous tendon rupture and tendonitis, acute liver failure or serious liver injury(hepatitis, QTc prolongation /torsadesdepointes, toxic epidermal necrolysis (TEN), and Stevens–Johnson syndrome, severe central nervous system  disorders  (CNS) and Clostridium  difficile associated  disease (CDAD pseudo membranouscolitis), as well as photosensitivity/phototoxicity reactions. Psychotic reactions and confusional states, acute pancreatitis, bone marrow depression, interstitial nephritis and hemolytic anemia may also occur during ciprofloxacin therapy. Additional serious adverse reactions include temporary, as well as permanent, loss of vision, irreversible double vision, drug induced psychosis and chorea (involuntary muscle movements), impaired colorvision, exanthema abdominal pain, malaise, drug fever, dysaesthesia and eosinophilia.

 

Polymer Profile

1. Sodium alginate⁶⁴

Synonyms                   :           og1; ALGIN; minus; tagat; Aigin; kelgin; kelgum;                                                    kelset; keltex; amnucol

Functional category  :           Stabilizer, thickener, gelling agent, emulsifier

Chemical structure:

 

 

 

Description: Occurs as white to yellowish brown filamentous, grainy, granular or  powdered forms.

Solubility:  It is slowly soluble in water, forming a viscous, colloidal solution. It is insoluble in alcohol and in hydro-alcoholic solutions in which the alcohol content is grater than 30% by weight. It is also insoluble in other organic solvents.

Melting Point:  >300°C (572°F)

Stability and Storage conditions: It is hygroscopic. Dry storage stability is excellent when the powder is stored in a well-closed container at temperatures of 25^o C or less.            

Handling Precautions: Keep away from heat. Keep away from sources of ignition. Empty containers pose a fire risk, evaporate the residue under a fume hood. Ground all equipment containing material. Do not ingest. Do not breathe dust. If ingested, seek medical advice immediately and show the container or the label. Keep away from incompatibles such as oxidizing agents, acids, alkalis.

Safety: The incorporation of 5 to 15% sodium alginate in the diet of pure breed beagle dogs for one year caused no harmful effects. It is found not allergenic.

2. CARBOPOL 934 P⁶⁴

 

Figure 9: Structure of Carbopol 934 P

Synonyms

            Acrypol;          Acritamer;       acrylic  acid     polymer;          carbomera; Carbopol;carboxy polymethylene; polyacrylic acid; carboxyvinyl polymer; Pemulen; Tego Carbomer.

Chemical Name and CAS Registry Number

Carbopol

Functional Category

            Bioadhesive    material;          controlled-release        agent;  emulsifying agent; emulsion stabilizer; rheology modifier; stabilizing agent; suspending agent; tablet binder.

 

Description

            Carbopol are white-colored, ‘fluffy’, acidic, hygroscopic powders with a characteristic slight odor. Typical Properties Acidity/alkalinity pH = 2.5–4.0 for a 0.2% w/v aqueous dispersion; pH = 2.5–3.0 for Acrypol 1% w/v aqueous dispersion. Density (bulk): 0.2 g/cm3 (powder); 0.4 g/cm3 (granular). Density (tapped): 0.3 g/cm3 (powder); 0.4 g/cm3 (granular). Dissociation constant: pKa = 6.0_0.5

Melting point: Melting point of Carbopol is 100-1050C.

Solubility Swellable:

            In water and glycerin and, after neutralization, in ethanol (95%). Carbomers do not dissolve but merely swell to a remarkable extent, since they are three- dimensionally cross linked micro gels.

Viscosity:

            Carbopol 934 P is a high molecular weight polymer of acrylic acid cross linked with allyl ether of pentaerythritol. Carbopol 934 P , previously dried in vacuum at 80 for 1h, contains not less than 56.0 percent and not more than 68.0 percent of carboxylic acid (-COOH) groups. The viscosity of a neutralized 0.5 percent aqueous dispersion of carbomer 934 P  is between 40,000 an 60,000 centipoises.USP30-NF25.

Applications in Pharmaceutical Formulation or Technology

            Carbopol 934 P  are used in liquid or semisolid pharmaceutical formulations as rheology modifiers. Formulations include creams, gels, lotions and ointments for use in ophthalmic, rectal, topical and vaginal preparations.  In tablet formulations, carbomers are used as controlled release agents and/or as binders. In contrast to linear polymers, higher viscosity does not result in slower drug release with carbomers. Lightly crosslinked carbomers (lower viscosity) are generally more efficient in controlling drug release than highly crosslinked carbomers (higher viscosity). In wet granulation processes, water, solvents or their mixtures can be used as the granulating fluid.  The  tackiness  of  the  wet  mass  may  be  reduced  by  including  talc  in  the formulation or by adding certain cationic species to the granulating fluid. Carbomer polymers have also been investigated in the preparation of sustained-release matrix beads. Carbomers are also used in cosmetics. Therapeutically, carbomer formulations have proved  efficacious  in  improving  symptoms  of  moderate-to-severe  dry  eye syndrome.

 

3. SODIUM BICARBONATE^64,

1. Non-proprietary Names

      BP: Sodium bicarbonate.

      Ph. Eur: Natrii hydrogenocarbonas.

      USP: Sodium bicarbonate.

2. Synonyms: Baking soda; E500; monosodium carbonate; sodium acid

      Carbonate: sodium hydrogen carbonate.

3. Chemical Name: Carbonic acid monosodium salt.
4. Empirical Formula: NaHCO3
5. Molecular Weight: 84.01
6. Functional Category: Alkalizing agent; therapeutic agent.
7. Description: Sodium bicarbonate occurs as an odorless, white crystalline powder with a saline, slightly alkaline taste. The crystal structure is monoclinic prisms. Grades with different particle sizes, from a fine powder to free flowing uniform   granules, are commercially available.
8. Solubility: Practically insoluble in Ethanol (95%) and Ether. Soluble in water.
9. Stability and Storage condition: Sodium bicarbonate is stable in dry air but slowly decomposes in moist air should therefore be stored in a well-closed      container in a cool, dry, place.
10. Safety: Sodium bicarbonate is metabolized to the sodium cation, which is eliminating from the body by renal excretion, and the bicarbonate anion, which becomes part of the body’s store. Any carbon dioxide is eliminated via the lungs. Administration of excessive amounts of sodium bicarbonate may thus disturb the body’s electrolyte balance leading to metabolic alkalosis or possibly sodium overload potentially serious consequences. Orally ingested sodium bicarbonate neutralizes gastric acid with the evolution of carbon dioxide and may cause stomach cramps and flatulence. When used as excipients, sodium bicarbonate is generally regarded as an essentially nontoxic and non irritant material.

 

4. LACTOSE⁶⁴

Functional category: Tablet and capsule diluent

Chemical Name: 4-O- β-D galactopyranosyl-α-D-glucocpyranose,

Emperical formula:  C₂₂H₂₂O₁₁

Description: White to off white crystalline particles or powder, odourless and slightly sweet tasting.

Solubility: Freely soluble in water, practically insoluble in chloroform, ethanol and ether.

Stability and storage conditions: Under humid conditions (80%RH and above) mold growth may occur. It should be stored in a well closed container in a cool, dry place.

Incompatibilities: A millard type condensation reaction is likely to occur between lactose and compounds with a primary amine group to form brown coloured products.

Applications in pharmaceutical formulation or technology:

            As filler or diluent in tablets (wet granulation and direct compression) and capsules, in lyophilized products and infant fed formulas.

 

5. MAGNESIUM STEARATE⁶⁴

Non- proprietary Name: NF: Magnesium Stearate, BP: Magnesium Stearate

Synonyms: Metallic stearic, Magnesium salt.

Functional category: Tablet and capsule lubricant

 

Chemical Names: Octadecanoic acid; Magnesium salt; magnesium Stearate.

Structural Formula:

                       

 

Emperical Formula: C₃₆H₇₀MgO₄

Molecular Weight: 591.3

Description: It is a fine, white, precipitated, or milled, impalpabale powder of low bulk density, having a faint characteristic odour and taste. The powder is greasy to touch and readily adheres to the skin.

Typical properties:

Solubility Practically insoluble in ethanol, ethanol (95%), ether and water, slightly soluble in benzene and warm ethanol (95%)

Stability and storage conditions: Stable, non-self polymerizable. Store in a cool, dry place in a well closed container.

Applications in Pharmaceuticals Formulation or Technology:

Tablet and capsule lubricant, glidant and antiadherent in the concentration range of 0.25-2.0%.

 

6. PVP K 30 ⁶⁴:

Synonym: Pvpp, Polyvidone, Povidone, Vinylpyrrolidone, Vinylbutyrolactam, Crospovidone, Neocompensan, Hemodesis, Kollidon, Luviskol, Periston, Peviston, Plasdone, Plasmosan, Protagent, Subtosan, Bolinan, Hemodez, Polygyl, Sauflon.

Chemical name: Poly (1-vinyl-2-pyrrolidinone)

Description: PVP is soluble in water and many organic solvents and it forms hard, transparent, glossy film. It is compatible with most inorganic salts and many resins. PVP stabilizes emulsions, dispersions and suspensions.

Applications:

1. Cosmetics: PVP K-30 can be used as film forming agent, viscosity enhancement agent, lubricator and adhesive. They are the key component of hair sprays, mousse, gels and lotions & solution. They are also convenience assistant in skin care product, hair-drying reagent, shampoo, eye makeup, lipstick, deodorant, sunscreen and dentifrice.
2. Pharmaceutical: Povidone K 30 is a new and excellent pharmaceutical excipient. It is mainly used as binder for tablet, dissolving assistant for injection, flow assistant for capsule, dispersant for liquid medicine and pigment, stablizer for enzyme and heat sensitive drug, co precipitant for poorly soluble drugs, lubricator