Semi-solid /solid Formulations🧴 Flashcards
5 skin functions
Protective barrier
Prevents water loss
Sensory function
Thermoregulation
Site of vitamin D synthesis
According to Flicks law how can we improve drug delivery and what are the corresponding strategies? (2 ways)
1) Increase Diffusion coefficient
2) Increase concentration gradient
Biological factors affecting percutaneous absorption
Physiochemical factors affecting percutaneous absorption
Define and describe the two types of cream composition
• Creams: Semi-solid emulsions, typically a mix of oil and water.
Two Types:
Oil-in-water (O/W): Water is the continuous phase, non-greasy, easy to wash off.
• Water-in-oil (W/O): Oil is the continuous phase, more occlusive, better for dry skin.
Advantages of creams
Moisturizing effect: Hydrates the skin and softens the stratum corneum.
Enhanced Drug Absorption: Creams can facilitate the penetration of active ingredients.
Patient Compliance: Non-greasy texture, easy to apply, and pleasant feel.
Versatile: Suitable for various drugs (anti-inflammatory, antifungal, antibiotics).
Mechanism of cream drug delivery
Drug Release: The drug diffuses from the cream matrix into the skin.
Barrier Penetration: Moisturizing properties help overcome the skin barrier (stratum corneum).
Occlusive (‘blocking’) Effect (W/O creams): Traps moisture, increasing skin hydration and permeability.
Factors influencing cream drug delivery
Cream Composition: Emulsion type (O/W vs. W/O). lipid content.
Drug Properties: Solubility, molecular weight, lipophilicity.
Skin Condition: Intact vs. damaged skin, hydration levels.
Cream excipients and role
Water: Solvent for hydrophilic ingredients; hydrates the skin and forms the base for oil-in-water emulsions.
Oils/fats: Provide emollient eftects, soften skin, and form the base for water-in-Oil emulsions; dissolve lipophilic drugs.
Emulsifying agents: Stabilize oil-water mixtures and prevent separation (e.g., cetyl alcohol, polysorbates).
Thickening agents: Increase viscosity for better texture and spreadability (e.g.. carbomers, cetyl alcohol)
Humectants: Retain moisture in the skin (e.g., glycerin, propylene glycol).
Preservatives: Prevent microbial growth, extending shelf life (e.g., parabens, phenoxyethanol).
Penetration enhancers: Increase drug absorption through the skin (e.g., ethanol, propylene glycol).
Gel definition and describe two types
Semi-solid systems with three-dimensional matrix that traps a liquid or semi-liquid phase.
Types:
Hydrogels (water-based)
Organogels (organic solvent-based)
Advantages of gels (4) (hydrogels)
Enhanced drug release: Gels can provide controlled or sustained release of drugs. ( by networks cross linking with different molecules, making it more stiff so we can control the drug release)
High patient compliance: Easy to apply, non-greasy, and comfortable on the skin.
Targeted drug delivery: Suitable for topical (e.g., diclofenac gel), transdermal (e.g., testosterone gel), ophthalmic (e.g., pilocarpine gel for glaucoma), and other applications.
Good penetration: Better drug permeation through the skin due to increased hydration.
Non-greasy, high patient compliance.
Good for burns and moist environments.
Effective for topical, transdermal, and ophthalmic delivery.
Challenges of gels (3)
Stability issues: Gels may be sensitive to temperature changes
Compatibility: Drugs and excipients should be compatible with the gel matrix.
Limited use with hydrophobic drugs: aggregation (reduces solubility). Hydrogels may not be suitable for lipophilic drugs.
Gel excipients and role
- Gelling Agents
Create and stabilize the gel structure (e.g., carbomers, xanthan gum). - Solvents
Dissolve active ingredients (e.g., water, alcohol). - Humectants
Retain moisture in the gel and skin (e.g.., glycerin, sorbitol). - Preservatives
Prevent microbial growth (e.g., phenoxyethanol, parabens). - pH Adiusters
Maintain optimal pH for stability and skin compatibility (e.g., citric acid). - Stabilizers
Prevent degradation and separation (e.g., antioxidants like vitamin E). - Penetration Enhancers
Improve drug absorption through the skin (e.g., ethanol, DMSO). - Thickening Agents
Adjust viscosity and texture (e.g., cellulose derivatives).
Ointments definition
Less water than creams - greasy feeling
Semi-solid preparations with a high oil content, used for local or systemic delivery, providing prolonged skin contact and moisturizing effects.
Ointment excipients and role
Vehicle/Base: Forms the main structure of the ointment: provides a medium for the
API. Types include oleaginous (e.g., petrolatum), absorption, water-removable, and water-soluble bases. More oil than water (opposite from the creams)
Stabilizers: Preserve API stability and prevent degradation. Examples include antioxidants (e.g., BHT:Butylated Hydroxytoluene) and preservatives (e.g., parabens).
Penetration Enhancers: Increase skin permeability to enhance API absorption.
Examples include ethanol and dimethyl sulfoxide (DMSO).
Emulsifiers: Facilitate mixing of oil and water phases in emulsions. Examples include sorbitan esters and polysorbates.
Thickeners: Adjust the viscosity and consistency for ease of application. Examples include hydroxyethyl cellulose and carbomers.
Humectants: Attract and retain moisture in the skin to enhance hydration. Examples include glycerin and hyaluronic acid.
Advantages of ointments (3)
Enhanced Skin Contact: Prolonged retention and contact with the skin. ( not easy to wash off with water or sweat)
Moisturizing Effect: Useful for dry or rough skin conditions.
Versatility: Can be formulated for various therapeutic purposes.
Challenges of ointments
Patient Acceptance: Ointments can be greasy and may stain clothing.
Stability: Formulation stability over time.
Penetration: Limited for drugs with low skin permeability
Benefits of pastes
Protective barrier: Forms a barrier on the skin to
protect against irritants or infections.
Localised action: Delivers the API directly to the affected area, enhancing the therapeutic effect.
Enhanced stability: Thicker consistency reduces the risk of the API being washed away or diluted.
Paste excipients and role
Active Pharmaceutical Ingredient (API)
Therapeutic Effect: Provides the intended therapeutic effect, such as anti-inflammatorv or antimicrobial action.
Base (vehicle)
Medium: The foundation of the paste, providing the bulk and consistency.
Often includes agents like petrolatum, lanolin, or waxes. Oily not water base.
Thickening agents
Consistency: Enhance the paste’s viscosity to ensure it remains in place upon application. Examples include clays (bentonite), starches, or cellulose
derivatives.
Emollients
Skin Softening: Help to soften and smooth the skin, improving the application and feel of the paste. Examples include lanolin and various oils.
Preservatives
Stability: Prevent microbial growth and extend the shelf life of the paste.
Common preservatives include parabens or phenoxyethanol.
Stabilisers
Formulation Intearity: Maintain the physical and chemical stability of the paste over time. This can include agents that prevent phase separation or degradation.
Creams excipients and role (specific)
Distilled water: Solvent for hydrophilic ingredients, hydrates skin and forms base for oil in water emulsions
Cetostearyl Alcohol (emulsifying and thickening agent): Stabilises oil-water mixtures and prevents separation and provides a moisturising effect.
Liquid Paraffin: Emollient. Moisturiser that softens and smooths the skin by forming a barrier to prevent moisture loss.
Chlorocresol: Preservative that prevents microbial growth
Macrogol cetostearyl ether: Surfactant that contributes to the hydration of the skin by forming a barrier that helps to reduce water loss
White soft paraffin: Base. Emollient. Provides occlusivity and helps with skin hydration. Emollient properties for moisture barrier.
Sodium Dihydrogen Phosphate Dihydrate: buffer system
Glycerine: humectant. Draws moisture into skin & prevents dryness.
Phosphoric Acid: PH adjuster
Sodium Hydroxide: Balance and maintain pH levels
Zinc oxide paste (the product): paste provides protective barrier and mild antiseptic to provide soothing and promote healing.
Ointment specific components and role
Castor oil: preservative, prolongs shelf life, antimicrobial. Hydrogenated one traps moisture abs helps moisture skin to enhance absorption.
Why are creams good?
Effective for inflamed skin conditions: combines nydraung. emollient, and anti-inflammatory properties. The ointment base allows for a prolonged retention time on the skin, enhancing the efficacy of the drug.
Why are ointments good?
The high oil content provides a barrier, making it suitable for treating fungal infections on dry, cracked skin.
Why are pastes good?
Provides a thick. protective barrier ideal for conditions needing moisture protection, such as diaper rash.
Why are transdermal patches good?
Offers controlled nicotine release, enabling steady absorption through the skin into the bloodstream. This delivery svstem avoids the gastrointestinal tract, reducing potential side effects and ensure seaov olasma concentracions
How to improve drug delivery and strategies
1) Increase Diffusion Coefficient (D)
The diffusion coefficient depends on the physicochemical properties of the drug (e.g., molecular size, solubility, and polarity) and the nature of the skin
B arrier
J = - D (AC(x,t)) / дх
Strategies:
Use of permeation enhancers: Chemicals like alcohols, fatty acids, or surfactants can disrupt the skin’s lipid structure and improve the fluidity of the stratum corneum (outermost skin layer), enhancing drug diffusion.
Lipid-based formulations: Liposomes and other vesicular systems can carry drugs through the skin’s lipid bilayer.
Nanoparticles: Nano-sized carriers (e.g., solid lipid nanoparticles, polymeric nanoparticles) can penetrate the skin more easily, improving drug transport.
2) Increase the concentration Gradient
• The driving force for diffusion is the concentration gradient, so increasing the drug concentration at the skin’s surface can improve delivery.
Strategies:
• Saturated formulations: Use formulations that maintain a high drug
concentration at the SurAce or SUStAined release over time
• Drug reservoirs: Use systems like transdermal patches that maintain a consistently high concentration over the application period.
• lontophoresis: Apply an electric current to increase drug movement by enhancing the concentration gradient
Ointment mechanism of delivery
Localized Delivery:
Direct application to the skin or mucosa.
Useful for treating conditions like eczema, psoriasis, or fungal infections.
Systemic Delivery:
Through skin absorption into the bloodstream.
Effective for drugs with high skin permeability.
Factors affecting ointment efficiency
Drug Penetration:
Molecular size and lipophilicity.
Formulation characteristics.
Skin Properties:
Hydration, temperature, and integrity of the skin.
Formulation:
Type of base used.
Concentration of active ingredients.
How can the absorption of a formulation be improved?
mucosa - use water base gel (surface is already hydrated)
- Enhancers
Fatty Acids: Disrupt lipid bilayers to increase permeability (e.g., oleic acid, linoleic acid).
Surfactants: Reduce surface tension for better penetration (e.g., sodium lauryl sulfate, polysorbate 80).
- Formulation Adjustments
pH: Adjust to match skin’s pH (~5.5) for better stability and absorption.
Viscosity: Increase to prolong skin contact; excessive viscosity may hinder absorption.
Osmotic Pressure: Optimize to reduce irritation and enhance drug release.
- Nanoparticles
Increased Surface Area: Smaller particles enhance skin contact and absorption.
Enhanced Penetration: Can bypass skin barriers for deeper delivery.
Controlled Release: Provide sustained therapeutic effects over time.
- Microneedles
Microchannels: Create channels in the skin, bypassing the stratum corneum.
Deeper Penetration: Deliver drugs to dermal layers, reaching blood and lymphatic vessels.
- Temperature
Increased Permeability: Mild heat enhances skin permeability.
Enhanced Blood Flow: Heat increases blood flow, improving drug uptake.
- Drug Solubility and Stability
Solubility: Enhanced solubility improves absorption.
Stability: Prevents degradation of the drug in the formulation.
- Patient Compliance
Formulations must be easy to apply and comfortable for regular use.
Based on the comparison between gel and cream formulations, describe how these two formulations should be modified to target either the mucosa or the skin.
Thick (viscosity)
Skin contact for a long time
API solubility - ensure ingredient easily solubilised in chosen formulation to absorb into skin tissue
Penetration enhancers (for lipid based to enhance penetration efficacy)
PH - PH must align with natural environment of mucosa or skin surface
Moisturising barrier enhancers - improved hydration of skin to enhance drug delivery eg humectants attract water to skin. Moisturising properties help overcome skin barrier (stratum corneum).
- Targeting Mucosal Delivery
Gel modification-
Bioadhesive polymers like carbomer, chitosan, or HPMC (HYDROXYPROPYL METHYLCELLULOSE) can increase mucosal tissues adherence and allow prolonged contact time
Reducing ethanol concentration minimises irritation on mucosal tissues, making the gel gentler and more suitable for sensitive areas.
Cream Modification
Emulsify using mild surfactants to minimise irritation on the mucosa and avoid greasy, heavy textures
pH should be adjusted to be closer to the natural pH of mucosal tissue (typically slightly acidic), ensuring comfort and compatibility with mucosal tissue. - Targeting Skin Delivery
Gel modification
Penetration enhancers like ethanol or propylene glycol to facilitate the transdermal delivery of active ingredients into the skin layers
Agents that dry quickly and leave a residue-free finish such as Cyclopentasiloxane ensures good patient compliance and a less greasy feel.
Cream Modification-
Increase the emollient content to enhance hydration and strengthen the skin’s barrier, helping the product stay on the skin longer
Using an oil-in-water (O/W) emulsion with penetration enhancers boosts the delivery of active ingredients while maintaining hydration and a comfortable feel on the skin.
Ointments
Less water content than creams
applied to areas such as palms and soles skin with short or sparse hair
drier areas of the body, such as the trunk & extremities, thickened & lichenified skin
occlusive effect, increases skin hydration, penetration & drug efficacy (occlusive = blocks water evaporation = hydration)
emollient properties soothe & soften the skin
water resistance increases contact time
fewer/no preservatives (no water > no microorganism growth)
greasy so cosmetically unappealing difficult to wash off
not flow well, more difficult to spread than creams, lotions & solutions
Rectal advantages
• The patient is unable to swallow. Eg if need to treat migraine and patient is vomiting
• The drug under consideration is not well suited for oral administration
>Gastrointestinal side effects
> Extensive first-pass and metabolism and enzymatic degradation in the GIT
> Vomiting
> Impaired consciousness
• Safe route
• For immediate and modified release (not sustained as lost when go to toilet
High blood supply
Rectal disadvantages
• Incorrect positioning of the dosage form can increase first pass metabolism
(Further up decreases bioavailability )
• Retention time (peristalsis of the rectal wall): diarrhoea would loose dose, constipation causes stool to effect dissolution & absorption
• Poor patient acceptability & adherence, especially for long-term
Weak buffering capacity
Low enzymatic activity
Low volume
Small area area (300cm^2)
Lack of villi and microvilli
Rectal delivery & first pass
Systemic Absorption and First Pass Effect:
> superior rectal vein empties into the inferior mesenteric vein and then into the portal system. > decreases bioavailability (first pass metabolism)
> middle and inferior rectal veins empty into the internal iliac vein and the inferior vena cava = systemic circulation = bypasses first pass metabolism, increases bioavailability therefore if absorbed through this area
As we can’t differentiate between them, we approximate 50% of the dose can bypass metabolism
General rectal fact: Rectum wall consists of a single layer of columnar epithelial cells together with the goblet cells (mucus secretion).
Vaginal drug delivery
PH 4-5 (to maintain area clear of infection, has normal flora, raising PH would be more prone to infection)
pH 4.5. (lactobacillus bacteria convert glycogen from epithelial cells into lactic acid
Clearance of vaginal fluid can affect dosage form retention in the vaginal cavity
Coated with mucus (cervicovaginal fluid)
provides lubrication & protection against infections
Mainly passive diffusion
Uterine first pass effect (goes to uterus from vagina)
Vaginally administered drugs directly transported to uterus
Leaky blood supply even though high
Drug will leak from venous blood supply to arteries then to uterus, not much
Vaginal advantages
• Local and systemic? drug delivery
• Avoids hepatic first-pass metabolism
• First uterine pass effect, vaginal route has potential for preferential delivery to the uterus, (uterine targeting of drugs e.g. progesterone)
• Suitable for vaccine administration (not yet approved)
• Suitable for microbicide delivery
• Self-administration and removal of dosage forms are relatively easy
Vaginal disadvantages
• Menstrual cycle and hormonal variations (eg age or secretion and thickness throughout cycle) affect rate and extent of absorption of drugs intended for systemic administration
• Drug release and availability of locally acting drugs can be influenced by interpatient variations in the volume of cervicovaginal fluids
• Dosage form retention can be problematic (cones with applicator and usually at night so stays for longer)
• Damage to the vaginal epithelium by the formulation can lead to infections (by ph changes)
• Privacy concerns and culture barriers
Suppositories bases
Fatty bases: for hydrophilic drugs
Water-soluble bases: for lipophilic drugs
This allows quick onset and allow the drug tonne released once dosage form has melted
Fatty vehicles:
> melt slightly lower than body temp
> narrow melting point range (solidifies promptly after preparation, preventing agglomeration or sedimentation of suspended drug particles & allows to dissolve rapidly in body)
> Cooling rate of molten vehicle should be slow to allow homogeneous solidification of all fatty materials as two phases would interrupt the dosage form
Water soluble bases:
Glycerinated gelatine- dissolves slushy in mucus, prolonged released.
>Not used rectally for drug delivery, as it has an osmotic effect and can stimulate evacuation. Glycerin suppositories are used, however, in the treatment of constipation (active ingredient in rectal not base)
>Used in vaginal pessaries, to prolong local action.
>May cause dryness and irritation with insertion as water will be drawn from the mucosal layer.
Polyethylene glycols (PEG)
• Varying molecular weight ranges available - designated by the number that follows PEG (mixing low & high is good, one to congeal base other to melt eg)
• Increasing PEG molecular weight increases melting point & decreases water solubility & hygroscopicity
• Increasing the molecular weight also increases viscosity
• Control the release of drug via controlled dissolution of PEG/PEG mixtures
• Can be more irritating to the mucosal membranes than fatty bases. To reduce irritation, PEG bases should contain at least 20% water; if not, patients should be instructed to dip the suppository in water prior to use to reduce stinging sensation upon insertion into the rectum
Suppository excipients
To prevent sedimentation in suspension suppository formulations (stokes law)
• Decrease particle size
• Increase viscosity of the formulation
• Reduce density difference between the drug particles and the suppository base
Stokes Law
v = d’(Ps -Py) g/18n
v = sedimentation rate (cm/s)
d = particle diameter (cm)
Ps* particle density (8/cm°)
p. = base density (g/cm’)
g = force of gravity 981 cm/s)
n = base viscosity P
Suppository manufacture / production
• Melt Moulding
Components are melted together, poured into a mould, allowed to cool & congeal on an industrial scale, the principles of injection moulding may be applied to melt moulding to extrude melted base into moulds under pressure
• Compression Moulding
A paste-like mixture of base & drug is forced into a mould under pressure, without the use of additional heat
Advantages include the use of heat labile drugs and also the incorporation of a higher loading of drugs that are insoluble in the base
Drug release from suppository base
• Melting or dissolution of the suppository base
• Diffusion of the drug from the suppository base
• Dissolution of the drug in the bodily fluids
Lipophilic drugs - slowly released from an oily base & moderately quickly released from a water-soluble base. Lipophilic drug will dissolve slowly once in the aqueous compartment of the rectum
Hydrophilic drugs - released rapidly from an oily base. Release from a water-soluble base is dependent on the rate of dissolution of the base and the rate of diffusion of the drug out of the base
Increased viscosity of the base decreases drug release. Viscosity of the base can be increased by adding greater amounts of fat or wax, or in the case of PEG bases, by using a higher molecular weight PEG
Suppository storage
Humidity
Example: glycerinated gelatine suppositories
• high humidity: absorb moisture from the atmosphere (turn liquid) (not good)
• low humidity: lose water and became brittle (not good)
Temperature
• cool temperatures to prevent softening of base (happens at less than 30 °C for cocoa butter bases, and less than 35 °C for glycerinated gelatin bases as at night body temp decreases) (fridge best)
• Suppositories containing PEG bases can withstand higher temperatures due to higher melting points (maintains shape)
Pessaries
Need high viscosity polymers
To increase localisation of drug in area especially as volume is 0.75ml at a time in the vagina
Control particle sizes to avoid irritation of vaginal membrane
Pessary advantages (vaginal tablet form)
• ease of storage
• ease of use
• Low cost
• well controlled large-scale manufacturing
• suitable for drugs susceptible to degradation in the presence of moisture
Pessary limitation (the vaginal tablet form)
• Dissolution of the formulation in the small volume of vaginal fluid (for this reason, vaginal tablets should be inserted as high as possible into the vagina)
Vaginal rings
• Ring-shaped diameter of ~ 50 - 70mm
• Flexible & often colourless dosage forms made from elastomeric polymers
• Drug reservoir within the polymer network allow controlled drug release over prolonged period
• Inserted with applicator & should be removed at the end of drug administration period if they are made from nonbiodegradable polymers such as silicone
• Poly(ethylene-co-vinyl acetate), silicone, and polyurethane polymers are the primary materials used in the fabrication of vaginal rings
• Balancing mechanical flexibility & strength of an IVR are needed to permit insertion and retention within the vaginal cavity without causing tissue abrasion
Not biodegradable so not environmentally friendly
Pessary excipients (vaginal tablet form)
• Excipients such as bicarbonate, together with an organic acid for carbon dioxide release, can be added to increase tablet disintegration, if necessary
• A good filler in the formulation of vaginal tablets is lactose, because it is a natural substrate for the vaginal microflora that converts lactose into lactic acid, retaining the vaginal pH within its normal range. Example Canesten (clotrimazole) pessaries contain lactose monohydrate and lactic acid (basically good filler that maintains PH to prevent infections)
• Other excipients used in vaginal tablet formulations include lubricants, glidants, binders and polymers for modified drug release, as for oral tablets
• Inclusion of mucoadhesive polymers such as Carbopol and xanthan gum in the formulation is desirable to minimize leakage and increase retention of the dispersed or dissolved tablet (Increases viscosity)
BSC classses
Class I: high solubility & high permeability
Class II: low solubility & high permeability
Class III: high solubility & low permeability
Class IV: low solubility & low permeability
Types of vaginal ring drug loading
Matrix (all of it containing drug)
Reservoir (empty polymer - drug)
Sandwich (empty polymer-drug-polymer)
Modified release Pessary example
Gyno-Pevaryl 150 mg
Vaginal Pessaries
Active Ingredient:
econazole nitrate
List of excipients:
• Wecobee M
• Wecobee FS
BCS II
If want local, slower release , same base with drug eg lipophilic drug in lipophilic base to prolong & maximise contact time with area & treat infection eg econazole (anti fungal) with wecobee M/ FS (lipophilic base)
* not sustained*
Suppository example
Dulcolax 5 mg
Suppositories
Active Ingredient:
Bisacodyl - constipation
List of excipients:
•• Hard fat (Adeps solidus)
BCS I
Laxative > want fast action
BCS class I = high solubility (water soluble drug)
Hard fat as base
Allows quick onset
Suppository example (tablet)
Paracetamol
1000mg
Suppositories
Active Ingredient:
• Paracetamol
List of excipients:
• Hydrogenated at
• Soyabean lecithin
BCS III
Want quick action > lecithin
Reduces agglomeration
Enhances spreadability
Increases onset of action
Suppository & Pessary summary
• Suppositories & pessaries are solid dosage forms suitable for local & systemic drug delivery
• The API is either dissolved or dispersed in a suitable base that can be soluble or dispersible in water, or it may be fatty and melt at body temperature
• Some companies refer to vaginal tablets and capsules as pessaries, making it crucial to understand the excipients used to differentiate between pessaries and vaginal tablets/capsules
• Vaginal rings are prepared with nonbiodegradable polymers and are designed for prolonged drug delivery over several weeks
Q: Describe the structure of the skin.
A: The skin has two main layers:
Epidermis: Provides barrier and protection, composed of keratinocytes.
Dermis: Provides support and flexibility, composed of collagen and elastin.contains blood vessels (systemic delivery if penetrated)
Q: What are the routes for delivering drugs through the skin?
Transepidermal:
Intercellular: Drug moves between cells.
Transcellular: Drug moves through cells.
Transappendageal:
Through sweat glands and hair follicles.
Q: What is Fick’s Law of Diffusion?
A: Molecules move from a region of high concentration to a region of low concentration, determined by factors like diffusion coefficient, concentration gradient, and distance.
Q: How can drug delivery through the skin be improved?
Increase diffusion coefficient (e.g., permeation enhancers, lipid-based formulations).
Increase concentration gradient (e.g., higher drug concentration in the formulation).
Disrupt skin barriers (e.g., electric currents like iontophoresis).
Q: What are the two types of cream emulsions?
Oil-in-water: Non-greasy, easy to wash off, good for normal skin.
Water-in-oil: Occlusive, traps moisture, ideal for dry skin.
Q: What factors affect drug delivery through the skin?
Biological factors: Skin thickness, hydration, temperature, age, and condition.
Physicochemical factors: Molecular weight, lipophilicity, solubility, pH, and formulation type.
Q: What excipients are commonly used in semi-solid formulations?
Water: Base for hydration and emulsions.
Oils: Provide emollient effects, dissolve lipophilic drugs.
Emulsifying agents: Stabilize mixtures.
Thickening agents: Control viscosity.
Humectants: Retain moisture.
Preservatives: Prevent microbial growth.
Penetration enhancers: Improve drug absorption.
How can the absorption of a formulation be improved?
mucosa - use water base gel
Enhancers: they are added to the formulation to increase the permeability of the skin. They can be incorporated into creams, gels, ointments, or patches.
Fatty Acids: can disrupt lipid bilayer of skin → increasing permeability (e.g. oleic acid, linoleic acid)
Surfactants: reduce surface tension for better penetration of the drug into the skin e.g. sodium lauryl sulfate and polysorbate 80.
Formulation Adjustments: changes made to the formulation itself
pH: Adjusting pH of the formulation to match the skin’s pH (around 5.5) can improve drug stability and absorption, match pka to enhance its ionisation state which may promote better absorption
Viscosity: Increasing it can prolong contact time with the skin, enhancing absorption. Excessive viscosity can hinder penetration
Osmotic Pressure: optimise to prevent irritation and improve drug release from formulation.
Nanoparticles: improve drug delivery. They can be encapsulated in liposomes or other carriers
Increased Surface Area: Smaller particles have a larger surface area, leading to increased contact with the skin and improved absorption
Enhanced Penetration: Nanoparticles can penetrate deeper into the skin layers, bypassing the skin barrier
Controlled Release: Nanoparticles can be designed to release the drug slowly over time, providing sustained therapeutic effects.
Microneedles: used as a separate device to deliver the drug. The drug can be loaded into the microneedles or applied to the skin after microneedle application.
Microchannels: Microneedles create tiny channels in the skin, bypassing the stratum corneum, the outermost layer of the skin (major barrier to drug absorption)
Deeper Penetration: Microneedles can deliver drugs to deeper layers of the skin, such as the dermis, where blood vessels and lymphatic vessels are located.
Temperature: Heat can be applied to the skin before or during drug application to enhance absorption. This can be done using a heating pad or a warm compress
Increased Permeability: Mild heat can increase skin permeability, allowing for better drug absorption
Enhanced Blood Flow: Heat can increase blood flow to the skin, facilitating drug uptake into the bloodstream.
Drug Solubility: The solubility of the drug in the formulation is crucial for absorption. Increasing solubility can improve absorption.
Drug Stability: The formulation should be stable to prevent degradation of the drug.
Patient Compliance: The formulation should be easy to apply and comfortable to use to ensure patient compliance.
