Semi-solid /solid Formulations🧴 Flashcards

Question

Why are transdermal patches good?

Answer 1

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

Answer 2

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

Answer 3

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.

Answer 4

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.

Answer 5

mucosa - use water base gel (surface is already hydrated) 1. 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). 2. 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. 3. 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. 4. Microneedles Microchannels: Create channels in the skin, bypassing the stratum corneum. Deeper Penetration: Deliver drugs to dermal layers, reaching blood and lymphatic vessels. 5. Temperature Increased Permeability: Mild heat enhances skin permeability. Enhanced Blood Flow: Heat increases blood flow, improving drug uptake. 6. Drug Solubility and Stability Solubility: Enhanced solubility improves absorption. Stability: Prevents degradation of the drug in the formulation. 7. Patient Compliance Formulations must be easy to apply and comfortable for regular use.

Answer 6

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). 1. 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. 2. 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.

Answer 7

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

Answer 8

• 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

Answer 9

• 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

Answer 10

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).

Answer 11

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

Answer 12

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

Answer 13

• 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

Answer 14

• 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

Answer 15

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

Answer 16

• 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

Answer 17

• 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

Answer 18

• 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

Answer 19

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)

Answer 20

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

Answer 21

• ease of storage • ease of use • Low cost • well controlled large-scale manufacturing • suitable for drugs susceptible to degradation in the presence of moisture

Answer 22

• 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)

Answer 23

• 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

Answer 24

• 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)

Answer 25

Class I: high solubility & high permeability Class II: low solubility & high permeability Class III: high solubility & low permeability Class IV: low solubility & low permeability

Answer 26

Matrix (all of it containing drug) Reservoir (empty polymer - drug) Sandwich (empty polymer-drug-polymer)

Answer 27

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*

Answer 28

Laxative > want fast action BCS class I = high solubility (water soluble drug) Hard fat as base Allows quick onset

Answer 29

Want quick action > lecithin Reduces agglomeration Enhances spreadability Increases onset of action

Answer 30

• 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

Answer 31

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)

Answer 32

Transepidermal: Intercellular: Drug moves between cells. Transcellular: Drug moves through cells. Transappendageal: Through sweat glands and hair follicles.

Answer 33

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.

Answer 34

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).

Answer 35

Oil-in-water: Non-greasy, easy to wash off, good for normal skin. Water-in-oil: Occlusive, traps moisture, ideal for dry skin.

Answer 36

Biological factors: Skin thickness, hydration, temperature, age, and condition. Physicochemical factors: Molecular weight, lipophilicity, solubility, pH, and formulation type.

Answer 37

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.

Answer 38

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.