Isoprenaline Aerosol Inhalation

Aerosol Inhalation

• Aerosols are dosage forms where a unit dose contains a medicament in suspension, delivered by a propellant.
• Propellants include dichloro-difluoro tetramethane and dichloro-tetrafluro tetramethane
• Aerosols could contain surface active agents, stabilizing agents, and other adjuvants.
• Aerosol inhalation devices consist of an aerosol dispenser with a metering valve to precisely control the amount of medicament delivered under pressure.
• Examples of aerosol inhalations include Isoprenaline, Salbutamol, Sodium chromoglycate, and Benzoin inhalation B.P.

Assay of Isoprenaline Aerosols Inhalation

• The assay involves the formation of a complex through the reaction of the phenol group of isoprenaline with iron salts.
• The color produced from this reaction is measured at 530 nm using a Vis spectrophotometer.
• Results are calculated from an average of 10 sprays.

Specification of Isoprenaline Aerosol Inhalations

• Particle size is an important part of specification for isoprenaline aerosol inhalation.
• The ideal size is 2-8 µm.
• Particles that are too small may be exhaled during breath.
• Particles that are too big may not reach the lung.

Capsules

• Capsules are shells that contain medication.
• Made of gelatin, capsules can be hard or soft.
• Hardness and softness depends on percentage content of glycerol or sorbitol solution.
• Capsules typically contain a single dose of the active ingredient.
• Capsules can be hard, soft, modified-release, or gastro-resistant.

Quality Control of Capsules

• Disintegration Test: Applicable to all capsules except modified-release types.
• Dissolution Test: Applicable to all types of capsules.
• Uniformity of Content: Applies to all types of capsules.
• Uniformity of Weight: Applies to all types of capsules.
• Determination of Active Ingredient: Achieved through chemical assay to determine the PAI.

Determination of Active Ingredient in Capsules

• Direct Method: Used for the assay of ingredients in dry capsules.
• Solvent Extraction Method: Used when the direct method is unsuitable.
• Digestion Method: Capsules are digested with acid and heat using 0.1N HCl in a water bath or autoclave, followed by filtration and application of the assay method.

Examples of Active Ingredient Assays in Capsules

• Examples include Clofibrate capsules (UV method), Ampicillin Capsules (HPLC method), Cephalexin Capsules (Iodimetric method), and Disopyramide Capsules (non-aqueous titration)
• Alcofenac Capsule Assay:
  • Sample: uses 20 capsules equivalent to 0.5g of alclofenac, dissolved with 100ml 96% neutralized ethanol
  • Measured using 0.1 M NaOH as the titrant
  • Endpoint indicated with ph.ph. indicator

Cough Capsules (Promethazine HCl)

• Consists of Promethazine HCl (36 mg), Noscapine (12.5 mg), and Ephedrine HCl (7.2 mg).
• The assay involves digesting with 0.1 M HCl, extracting the oil with ether, then extracting with 0.1N sulfuric acid after basifying the contents and extracting with ether.

Promethazine Hcl Assay

• Take an aliquot to determine promethazine HCl.
• Reactants: React with Palidium chlorate to produce an orange color, which is measured at 427 nm.

Noscapine Assay

• 10 ml noscapine is diluted to 100 ml water, then measured spectrophotometrically at 310 nm.

Ephedrine HCl Assay

• Ephedrine HCl has the same λmax as Noscapine.
• It is oxidized in an alkaline solution with (NaIO4 + NaHCO3) and extracted with sulphuric acid and cyclohexane.
• The extract's spectrophotometry is measured at 225 nm.

Creams

• Creams: semisolid dosage forms that contain 1+ drug substances dissolved or dispersed in a base
• Semisolid emulsions: oil-in-water (O/W) or water-in-oil (W/O)
• Uses: applying drugs to the skin (protective or therapeutic)

Quality Control Applied for Creams

• Microbial quality control
• Physical quality control
• Chemical quality control:
  • Determination of active ingredient: separation not needed if the base doesn't interfere.
  • Solvent choice is important to avoid lengthy procedures.
  • Examples: cetrimide cream; salicylic acid cream : sulphur cream
  • others separation should be done prior the assay

Cream Assays

• Dimethicone with Toluene.
• Hydrocortisone with Dehydrated ethanol.
• Nexenone with Ethanol.
• Proflavine with Chloroform/alcohol.
• In cases of small medicament concentration: extraction and separation, like with steroids.
• Spectrophotometric/titrimetric analysis: used for PAI detection after extraction.

Cetrimide Cream

• Sample preparation: Dissolve the cream in hot water, add sulfuric acid, chloroform, and a few drops of dimethyl yellow as an indictator.
• Analyte is Cetrimide
• Titrant: Dioctyl sodium sulfosuccinate
• An indicator of dimethyl yellow solution
• End point: A yellow color is obtained.
• Each 1ml Dioctyl sodium sulfosuccinate = 0.3364 Cetrimide

Eye Drops

• Eye drops: sterile dosage forms, solutions/suspensions of one or more components for therapeutic/diagnostic use in the conjunctional sac.
• They are sterile aqueous preparations with bactericides and fungicides.

Quality Control of Eye Drops

• Limit of particle size
• Sterility
• Chemical quality control
• Containers
• Labeling

Chemical Quality Control of Eye Drops

• Chemical assay: depends on the types of PAI in the eye drop.
• method: volumetric or instrumental (spectrophotometer/chromatographic).
  • Atropine: Gas chromatography
  • Chloramphenicol: UV spectroscopy at 278 nm
  • Pilocarpine: titration with cetyl pyridinim chloride with bromophenol blue as an indicator- HPLC in BP 2013.

Eye Ointments

• Ointments: sterile semisolid dosages for external use with solid/semisolid hydrocarbon base that melts around body temperature.
• Base: antioxidant, stabilizing agents, and antimicrobial preservatives
• Application: it decomposes into small drops when applied to the eye which stay for a long period of time in the conjunctival sac (increased drug bioavailability)

Assays

• Chloramphenicol Eye Ointment
  • Suspend 10mg of CPL in petroleum spirit, extract with water, and measure absorbance at 278 nm.
• Oxyphenbutazone Eye Ointment
  • Assay by UV at 254 nm
• Sulphacetamide Eye Ointment
  • Assay after extraction from the ointment base
  • Use amperometric titration with sodium nitrite

Ear Drops

• Ear drops can be liquids: a preparation, suspension, emulsion or solution of drugs in water, diluted alcohol, glycerin or polyethylene glycol for instillation into the ear.
• Due to the fatty secretions of the ear, aqueous solutions are not suitable.
• Ingredients: differ with the pupose

Sodium and Boric Bicarbonate Ear Drops Assay

• Sodium Bicarbonate Ear Drop:
  • Analyte: Sodium Bicarbonate
  • Solvent: Water
  • Titrant: 0.1 M standard hydrochloric acid
  • Indicator: Methyl orange solution, until red-orange
  • Reaction: Acid-Base, with 1 ml 0.1 M HCl equivalent to 8.401 mg of NaHCO3.
• Boric Acid Ear Drops:
  • Analyte: Boric Acid
  • Solvent: Water with mannitol,.
  • Titrant: 1M Standard sodium hydroxide,
  • Indicator: ph.ph solution
  • Endpoint: A pink color is obtained.
  • Reaction: acid-base, with 1ml 1 M NaOH = 61.8 mg H3BO3

Suppositories

• Solid preparations, administered in a single dose for local or systemic action.
• Medication is within a base, that liquifies at the body temperature

Quality Control for Suppositories

• Appearance,
• Uniformity of weight,
• Disintegration time,
• Chemical assay

Aminophylline Suppositories (USP-29)

• Assay for ethylinediamine:
• Preparation: Warm and reflux a volume of alcohol and ether.
• Analyte: Ethylinediamine.
• Titrant: 0.1N HCl.
• Endpoint: Detected by a modified calomel electrode.

Glycerol Suppositories (BP-2013)

• First dissolve sample in water, add bromocreasol indicator, then titrate with 0.1 M sodium hydroxide.
• Next, add sodium metaperiodate & propan 1,2-diol.
• Titrate produced formic acid using 0.1 NaOH to the same blue color as the sample.
• Remove excess sodium metaperiodate with propan-1,2-diol.

Tablets

• Solid pharmaceutical dosage forms which may be defined as containing drug substances with or without suitable diluents.
• Prepared by compression or moulding methods
• Administered through oral route

Quality Control of Tablets

• Weigh for uniformity of content,
• Test for disintegration, where appropriate,
• Check uniformity of content and lastly,
• Test for dissolution.

Co-Trimoxazole Tablets:

• Composition: sulfamethoxazole + trimethoprim
• Sample preparation: Dissolve in NaOH solution, then, extract trimethoprim with chloroform.
• Sulfamethoxazole Assay (titrmetric)
  • Analyte: Sulfamethoxazol.
  • Titrant: 0.1 N sodium nitrite.
  • Endpoint: amperometric detection
• Trimethoprim Assay (spectrophotometric)
  • Uv. Amax 271 nm.

Ointments

• Viscous or semisolid (external application) that includes medicinal substance dispersed inside it.
  • Hydrophobic or hydrophilic, Water emulsifying ointments
  • Main test: uniformity of content
  • Ex: beclomethazone oint, calamine ointment, salicylic acid ointment

Salicylic Acid Ointment (BP2013)

• Analyte: Salicylic acid.
• Solvent: Ethanol (96%), ether.
• Titrant: 0.1M sodium hydroxide.
• Indicator: Phenol red solution.
• Each mL of 0.1 M sodium hydroxide is equivalent to 13.81 mg of C7H6O3.

Injectable Preparations

• Sterile products with one or more components for injection, infusion, or implantation into the body.
• Forms: solution, suspension, emulsion, or reconstituted.
• Types: Injections, Intravenous infusions, and Powder for injections.

Quality Control of Injectable Preparations

• Uniformity of content and appearance
• Test for volume of liquid
• Test for pyrogen and bacterial endotoxin
• Test for sterility and leakage
• Clarity of solution
• Weigh for uniformity

Alprenolol and Cyanocobalamin Injections

• Alprenolol injection (UV- Spectrophotometric)
  • Take volume eq. to 5 mg of Alprenolol, add 5 ml of 0.1 N Hcl, and add water to produce 50 ml measure at 271 nm.
• Cyanocobalamin Injection
  • Dissolve 25 mg, dilute to 1000 ml water, measure absorbance at UV 361 nm.

Dextrose Intravenous Infusion

• Optical rotation test, test for particulate matter, pyrogens and acidity.

Elixirs

• Defined as: clear, liquid, flavored hydroalcoholic preparation intended for oral use.
• Consists of: one or more medicaments, sucrose, polyhdric alcohols & additives w(antimicrobials)

Elixir Assays

• Chloropheniramine elixir : Gas chromatography method.
• Pediatric paracetamol elixir
  • Use NaOH to dilute with water and then, filter measure absorbance with spectrophotometry at 257 nm (UV)

Syrups

• Syrups: are concentrated solutions of sucrose, other sugars or sweetening agents + polyhydric alcohol for prevent substance from crystallization .
• Can be treated same as elixir