Lecture Liquid Oral Dosage Forms 2024.pdf

Branko Radojkovic [email protected]  Liquid preparations for oral use are usually solutions, emulsions or suspensions containing one or more active substances in a suitable vehicle*; they may, however, consist of liquid active substances used as such (oral liquids) *vehicle n. (l...

Branko Radojkovic [email protected]  Liquid preparations for oral use are usually solutions, emulsions or suspensions containing one or more active substances in a suitable vehicle*; they may, however, consist of liquid active substances used as such (oral liquids) *vehicle n. (lat. vehiculum): any substance that acts as the medium in which a drug is administered. (Oxford Concise Medical Dictionary 9th ed.) British Pharmacopoeia 2024 (Ph. Eur. 11.5 update): Oral Liquids (Liquid Preparations for Oral Use, Ph. Eur. Monograph 0672)  Some preparations for oral use are prepared by dilution of concentrated liquid preparations, or from powders or granules for the preparation of oral solutions or suspensions, for oral drops or for syrups, using a suitable vehicle (e.g. reconstitution) British Pharmacopoeia 2024 (Ph. Eur. 11.5 update): Oral Liquids (Liquid Preparations for Oral Use, Ph. Eur. Monograph 0672) Liquid preparations for oral use may contain suitable antimicrobial preservatives, antioxidants and other excipients such as dispersing, suspending, thickening, emulsifying, buffering, wetting, solubilising, stabilising, flavouring and sweetening agents and colouring matter, authorised by the competent authority. *excipient n. (lat. excipere): a substance that is combined with a drug in order to render it suitable for administration; Excipients should have no pharmacological action themselves. (Oxford Concise Medical Dictionary 9th ed.) British Pharmacopoeia 2024 (Ph. Eur. 11.5 update): Oral Liquids (Liquid Preparations for Oral Use, Ph. Eur. Monograph 0672)  Oral solutions, emulsions and suspensions are supplied in single-dose or multidose containers. Each dose from a multidose container is administered by means of a device suitable for measuring the prescribed volume. The device is usually a spoon or a cup for volumes of 5 mL or multiples thereof, or an oral syringe for other volumes. British Pharmacopoeia 2024 (Ph. Eur. 11.5 update): Oral Liquids (Liquid Preparations for Oral Use, Ph. Eur. Monograph 0672)  Powders and granules for the preparation of oral solutions or suspensions are intended to be reconstituted with the prescribed liquid to produce a liquid preparation for oral use. They may contain excipients, in particular to facilitate dispersion or dissolution and to prevent caking. After dissolution or suspension, they comply with the requirements for oral solutions or oral suspensions, as appropriate. British Pharmacopoeia 2024 (Ph. Eur. 11.5 update): Oral Liquids (Liquid Preparations for Oral Use, Ph. Eur. Monograph 0672)  Oral drops are solutions, emulsions or suspensions that are administered as drops by means of a suitable device. Powders for the preparation of oral drops are intended to be reconstituted with the prescribed liquid to produce a liquid preparation for oral use. They may contain excipients to facilitate dissolution or suspension in the prescribed liquid or to prevent caking. After dissolution or suspension, they comply with the requirements for oral drops. Dose precision varies – may not be suitable if accurate dose is needed! British Pharmacopoeia 2024 (Ph. Eur. 11.5 update): Oral Liquids (Liquid Preparations for Oral Use, Ph. Eur. Monograph 0672)  Syrups are aqueous preparations characterised by a sweet taste and a viscous consistency. They may contain sucrose ≥ 45% m/m. Sweet taste can also be obtained by using other polyols or sweetening agents; Syrups usually contain aromatic or other flavouring agents Powders and granules for syrups are intended to be reconstituted with the prescribed liquid to produce a liquid preparation for oral use. They may contain excipients to facilitate dissolution. After dissolution, they comply with the requirements for syrups British Pharmacopoeia 2024 (Ph. Eur. 11.5 update): Oral Liquids (Liquid Preparations for Oral Use, Ph. Eur. Monograph 0672) In addition to the above requirements of the Ph. Eur. the following statements apply to any elixir, linctus, mixture that is the subject of an individual monograph in the BP: ELIXIRS are clear, flavoured Oral Liquids containing one or more active ingredients dissolved in a vehicle that usually contains a high proportion of Sucrose or a suitable polyhydric alcohol or alcohols and may also contain Ethanol (96 per cent) or a Dilute Ethanol. LINCTUSES are viscous Oral Liquids that may contain one or more active ingredients in solution. The vehicle usually contains a high proportion of Sucrose, other sugars or a suitable polyhydric alcohol or alcohols. Linctuses are intended for use in the treatment or relief of cough and are sipped and swallowed slowly without the addition of water. MIXTURES are Oral Liquids containing one or more active ingredients dissolved, suspended or dispersed in a suitable vehicle. Suspended solids may separate slowly on standing but are easily redispersed on shaking. British Pharmacopoeia 2024: Oral Liquids of the British Pharmacopoeia  Oral liquids are easily ingested by paediatric patients and those having difficulties swallowing or having an enteral feeding tube Dose flexibility Medicines with unpleasant taste Physical, chemical and microbiological stability Complex formulations Potential for unintentional overdose, especially with children Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Aqueous solutions: API/s are immediately available for absorption if taken on an empty stomach. If they precipitate in the acidic environment of the empty stomach the precipitation will often be so fine that it easily passes the closed pylorus and re-dissolves, after which rapid absorption is still possible. Suspensions: Dissolution of the API is the rate limiting step. The release/dissolution rate (and subsequent absorption) depends on many factors including solubility in vivo, the crystal modification and the particle size, and the viscosity of the suspension. Oily solutions and emulsions: Partition of the API from lipid phase into the aqueous phase is the rate limiting step. The release/partition rate depends on the solubility of the active substance in the lipid phase and the composition of the intestinal contents. The release and subsequent absorption of highly lipophilic APIs is generally slower as they reside mainly in the lipid phase. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Different oral liquid dosage forms offer the possibility to adjust the dosage form optimally to the requirements. Concentration of API/s should allow for precise dosing and age-appropriate dose volume (e.g. ≤ 5 mL for younger children, 5-10 mL for older children) Solutions, suspensions, emulsions or colloidal solutions/solubilisates. BP 2023: The vehicle for any preparation for oral use is chosen having regard to the nature of the active substance(s) and to provide organoleptic characteristics appropriate to the intended use of the preparation. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  high dosage accuracy and homogeneity if API is not sufficiently water-soluble, a solution may be achieved by adjusting the pH, by adding co-solvents or the use of a more soluble derivative (e.g. salt, ester) unpleasant taste may be difficult to mask (palatability)! insufficient chemical stability may be an issue (hydrolysis, oxidation)! Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  high dosage accuracy and homogeneity lipophilic (oil-soluble) APIs dissolved in non- polar or moderately polar oleaginous vehicles (e.g. plant/vegetable oils, triglycerides, synthetic and semi-synthetic esters) unpleasant oily taste (palatability) insufficient chemical stability (oxidation) may be an issue May cause oil aspiration/lipoid pneumonia! Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  API in solid form (particles) dispersed in the vehicle (ideally ≤ 0.1% dissolved) APIs with a very unpleasant taste can be processed better chemical stability in comparison to solutions insufficient physical stability may be an issue due to rapid sedimentation (particle size, viscosity) dosage accuracy may be problematic (potent medicines!) BP 2024: Suspensions may show a sediment, which is readily dispersed on shaking to give a suspension that remains sufficiently stable to enable the correct dose to be delivered. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Usually stabilised oil-in-water (O/W) dispersions APIs are dissolved in either aqueous or oily phase (or both) APIs in solid form (particles) may be dispersed in the vehicle (suspo-emulsion) better palatability in comparison to oily solutions Insufficient physical stability may be an issue due to emulsion instability (e.g. creaming, phase separation) dosage accuracy may be problematic due to poor homogeneity (CAUTION: potent medicines!) BP 2024: Emulsions may show evidence of phase separation but are readily redispersed on shaking. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Dissolved substances are more accessible and thus sensitive to degradation than if present as particles in suspension; most stability issues arise for that reason in aqueous solutions The two main degradation reactions are hydrolysis and oxidation The rate of hydrolysis is pH-dependent Oxidation is inhibited by removal of oxygen from water (e.g. boiling), reduction of headspace by completely filling of bottles, addition of a chelating agent for the removal of catalysing traces of metals and the addition of antioxidants. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Oral solutions can be physically unstable through crystallising of dissolved solids (e.g. temperature fluctuation, solvent evaporation, pH change) Suspensions are physically unstable preparations: sedimentation occurs at storage Emulsions may become non-homogenous during storage or can even ‘break’ (phase separation) Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer. BP 2023: In the manufacturing, packaging, storage and distribution of liquid preparations for oral use, suitable measures are taken to ensure their microbial quality Oral liquids – not sterile but must meet the pharmacopeial requirements Presence of certain micro-organisms in non-sterile preparations may have the potential to reduce or even inactivate the therapeutic activity of the product and has a potential to adversely affect the health of the patient. BP 2024 (Ph. Eur. 11.5): Appendix XVI D. Microbiological Quality of Non-sterile Pharmaceutical Preparations and Substances for Pharmaceutical Use Incompatibilities in oral liquids can take place between active substances and excipients, among active substances and among excipients Incompatibilities may cause chemical instability (e.g. chemical reaction, complexation), physical instability (e.g. precipitation, adsorption), or microbiological instability (precipitation of preservative, change of pH) Incompatibilities may occur due to localized high concentration of reactants - the order of dissolving and mixing should be so that no high concentrations are created during preparation. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Water is most commonly used vehicle for oral liquids Non-toxic, neutral taste, good solvent for polar APIs Water is a good growth medium for micro- organisms, so aqueous oral liquids generally have to be preserved. Water used in preparation of medicines is usually purified water, freshly boiled and cooled. Water has a low viscosity and high surface tension, which causes an uneven ‘flow’ when dosing the oral liquid from bottles and dosage devices; Thickening agents may be added to improve the flow Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Ethanol (ethyl alcohol, C2H5OH) is used as a co-solvent in a concentration up to 20 % in oral solutions ≥ 15 % v/v acts as a preservative not pharmacologically inert (CNS, sedation), drug-drug interactions not suitable in certain populations (paediatrics, cultural preferences, addiction disorders) WHO recommends ethanol to be avoided in oral preparations for children less than 6 years. Chronic exposure (>1 week) even in small doses, is in principle contraindicated in children < 6 years of age Small quantities sometimes present in flavours and preservatives Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Propylene glycol (1,2-propanediol or propane-1,2-diol) is used as a co-solvent in concentrations ~ 10-25% in oral solutions ≥ 15 % acts as a preservative Unpleasant taste The WHO has set a maximum permissible daily intake of propylene glycol as a food additive at 25 mg/kg EMA limit 1mg/kg (≤ 28 days) or 50mg/kg (1 month – 4 years) Because of the limited hepatic and renal function in preterm and term neonates the application of medicines containing propylene glycol may lead to accumulation and serious adverse effects following repeated administration or when administered in combination with another substrate of alcohol dehydrogenase (limiting step of metabolism) such as ethanol! Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Glycerol (glycerin, propane-1,2,3-triol) is used as co-solvent, preservative, sweetening agent and viscosity-increasing agent in concentration up to ~ 60 % sweetening power ~ 0.5 times that of sucrose ≥ 30 % acts as a preservative When used as an excipient or food additive, glycerin is not usually associated with any adverse effects and is generally regarded as a nontoxic and nonirritant material. The osmotic effect of high concentrations has to be considered in paediatrics and in patients with enteral feeding tubes because of gastrointestinal adverse effects (diarrhoea). Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Increasing the viscosity of water by the addition of thickening agents reduces the settling rate of particles in suspensions and stabilises O/W emulsions. sometimes referred to as suspending agents improving the flow of the oral liquid improving the palatability by shielding the taste buds from an unpleasant taste hydrophilic colloids In compounding mostly used in the form of mucilage (e.g. Methylcellulose mucilage 2% APF, Carboxymethylcellulose mucilage APF). Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Powders are sometimes difficult to wet which makes them difficult to disperse - they float on the liquid or form lumps, making it impossible to prepare homogenous suspension. Wetting Agents: ✓ Hydrophilic Excipients ✓ Surfactants Such a powder should be mixed with a hydrophilic substance before dispersion (e.g. glycerol, silicon dioxide) The addition of a surfactant to the aqueous phase can improve wetting as well Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Suspended particles may on storage settle into a compact sediment on the bottom of the bottle, which is impossible to re- suspend – an undesirable phenomenon known as ‘cakeing’ Flocculating agents are added to create an open and large volume sediment that can be resuspended easily In suspensions with negatively charged particles, multivalent cations (e.g. aluminium ions) may cause flocculation; on positively charged particles anions (e.g. Caking diagram showing controlled flocculation of a bismuth subnitrate suspension citrate ions) may also have this effect employing dibasic potassium phosphate as the flocculating agent. Credit: https://basicmedicalkey.com/emulsions-suspensions-and-related-colloidal-systems/ Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Typically, surface-active agents - surfactants Emulsions for oral use are predominantly of the o/w type; Emulsifying occurs by reducing the droplet size of the lipid phase and increasing the viscosity of the outer phase generally with use of a thickening agent Solubilisates are colloidal solutions of a liquid in another liquid that is not miscible with it; Fat-soluble liquid active substances can be solubilised using surfactants, whereby colloidal particles, micelles, are formed Surfactant films at the water–oil interface in o/w and w/o emulsions. Credit: https://basicmedicalkey.com/emulsions-suspensions-and- related-colloidal-systems/ Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  The pH of an aqueous oral liquid is important for the flavour, solubility and stability of the API/s, and for preservation. The preferred pH for an oral solution is between 5.5 and 7.5. A pH < 5.5 often tastes better but may degrade the tooth enamel; A pH above 8 often gives an unpleasant bitter/soapy taste solubility of active substances and excipients often depends on the pH The pH can affect the stability of an active substance or excipient (e.g. hydrolysis); There is often an optimal pH range for chemical stability Some antimicrobial preservatives are active only in certain pH range Acids and/or alkalis may be used for pH adjustment of oral solutions; If pH is critical, buffers may be used to precisely adjust pH The most used buffering agents in oral fluids are phosphates or citrates Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer. BP 2024: During development of a preparation for oral use whose formulation contains an antimicrobial preservative, the need for and the efficacy of the chosen preservative shall be demonstrated to the satisfaction of the competent authority. Water supports the growth of micro-organisms, therefore oral aqueous solutions, suspensions, emulsions and solubilisates in multidose containers should be preserved Preservatives may be used as well as excipients with preservative properties (e.g. ethanol, propylene glycol) The choice of the preservative is determined by the pH, the presence of antimicrobial co-solvents, the presence of a lipid or solid phase, and whether the liquid is intended for use in sensitive populations (e.g. neonates or children) Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer. Parabens (hydroxybenzoates) Esters of p-hydroxybenzoic acid methylparaben (methyl p-hydroxybenzoate) is widely used in oral liquids, alone or in combination with other parabens (e.g. propylparaben) esters - stable at pH 3 - 6. Decompose at pH ≥8 (hydrolysis) In oral liquids usually 0.1 - 0.15 % of the aqueous phase may cause allergic reaction (rarely) unpleasant taste General chemical structure of a paraben (a para-hydroxybenzoate) Weak estrogenic activity - xenoestrogens (activity where R = an alkyl group increases with length of the alkyl chain) Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer. Organic acids Benzoic acid, benzoates Sorbic acid, sorbates only effective in acidic pH (benzoates pH ≤ 5, sorbates pH ≤ 5.5) in oral liquids usually ≤ 0.2% of the aqueous phase benzoic acid/benzoates may cause allergic reactions benzoic acid/benzoates should be avoided in neonates Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer. Excipients with antimicrobial properties Propylene glycol ≥ 15 % (unpleasant taste, not quite as effective) Glycerol ≥ 30 % (less effective than propylene glycol, sweet taste) Sucrose preserves in concentrations ≥ 63 % m/v Ethanol preserves in concentrations ≥ 15 % v/v. If sufficient ethanol is present in oral preparations, no other preservatives are needed. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer. Chelating agents remove metal ions from aqueous solutions improve chemical stability of select medicines antimicrobial preservative synergists Antioxidants improve chemical stability (oxidation) of API/s and excipients reducing agents (mostly) water soluble, lipid soluble Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Taste of dissolved substance is much more pronounced than when present in oral solids. Unpleasant taste can be problematic, especially in paediatric patients! Taste masking in oral liquids is often needed to improve palatability of the medicine The unpleasant taste of an API (e.g. bitter, metallic) is masked in an oral liquid by the use of: ✓ sweetening agents ✓ flavours ✓ taste modifiers ✓ temperature (cold) ✓ viscosity enhancers Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Sweeteners ✓ sugars (sucrose, glucose, simple syrup) ✓ polyols – glycerol, sugar alcohols (sorbitol) ✓ artificial sweeteners (saccharin, cyclamate, acesulfame), ✓ natural sweeteners (stevia glycosides) Flavouring - taste + smell ✓ Fruit flavours ✓ Spices (anise, cinnamon, vanilla) ✓ Coffee/cacao/chocolate Taste modifiers: ✓ menthol (slight anaesthetic effect, cooling) ✓ NaCl (suppresses bitterness) ✓ bitterness inhibitors (some flavonoid compounds) adapted from: https://www.ajinomoto.com/umami/why-is-umami- important-to-us Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Colouring agents are primarily used to make the medicine more acceptable and appealing for the patient May be used to prevent mix-ups or misuse. Colouring agents may also used to protect light sensitive medicines or to prevent patients’ concerns about irrelevant degradations Only water-soluble colouring agents are processed in oral liquids (no pigments) Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  The preparation of oral liquids generally follows the basic operations such as weighing/measuring, particle size reduction/pulverisation, mixing, dispersing, dissolving, bottling The specific method depends on the characteristics of the formulation: solution, suspension, emulsion Small scale production (compounding) somewhat differs from large scale manufacturing (pharmaceutical industry) Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Compounding is usually manual, materials processed in mortar and pestle (pulverisation/trituration, levigation, preparation of suspensions and emulsions) or suitable laboratory glassware (solutions) Specialised machines are sometimes required (mixers, mills, homogenisers) If API/s are not available as raw material, commercially manufactured dosage forms are used as source of API/s (e.g. preparation of oral liquids from tablets or capsules) Pre-mixed excipients are often use (commercial or prepared in-house) After processing all materials, the liquid should be made up with the solvent to 100 % volume, preferably by using a measuring cylinder Product can be made gravimetrically/by weight if density of the liquid is known. Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.  Oral liquids are usually delivered in glass or plastic bottles; Generally brown glass is used to protect the content from light Oral suspensions and oral emulsions must be delivered in bottles that leave enough headspace for shaking The label must meet the requirements as mentioned in Therapeutic Goods Order No. 91 - Standard for labels of prescription and related medicines (commercially manufactured medicines) or the current edition of the APF (compounded medicines) Suspensions and emulsions – the label should state “shake well before use” Specific requirements for certain medicines (e.g. child resistant closure) Suitable measuring device (cup/syringe) must be provided Bouwman-Boer, Y., Fenton-May, V., & Le Brun, P. (2015). Practical Pharmaceutics : An International Guideline for the Preparation, Care and Use of Medicinal Products. Springer International Publishing : Imprint: Springer.