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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5441_Библиотеки_им_академика_М_И_Перельмана.pdf
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Additionally, it addresses the challenges associated with establishing bioequiva-
lence and meeting regulatory requirements for generic topical and transdermal
products. Furthermore, the chapter examines manufacturing challenges and the
need for process optimization and quality control. On the other hand, it also out-
lines the advances made in the eld, including the development of novel drug
delivery systems, personalized medicine, combination therapies, and continuous
monitoring and controlled release technologies.
Keywords
Transdermal · Topical · Bioavailability · Novel drug delivery · Controlled release
11.1 Introduction
Skin covers the major portion of the human body which consists of 15% of the total
body weight with a 2 m
2
surface area. Three layers make up the skin structure,
namely, epidermis, dermis, and hypodermis. The skin is a dynamic organ with
numerous specialized cells and processes. It maintains homeostasis with the help of
collecting sensory information from environment and plays a vital role in defense
mechanism toward pathogens (Tortora and Derrickson 2018; Tapfumaneyi etal.
2022). It is also involved in maintaining the proper temperature for the body to func-
tion well. Natural and synthetic topical products are frequently used to treat the
appearance of the face and abnormal condition of the skin (Domínguez-Hüttinger
etal. 2013). The treatment via the transdermal method of some dermatological dis-
eases such as alopecia, dermatitis, psoriasis, acne vulgaris, vitiligo, and skin cancer
may also be used for other diseases such as diabetes, osteoporosis, rheumatoid
arthritis, and Alzheimer’s and Parkinson’s disease (Rabiei etal. 2020).
Transdermal and topical pharmaceuticals are prescribed and administered rou-
tinely all over the world (Alany 2017). On the contrary, conventional skin formula-
tions are overpowered that are intended for topical, regional, and transdermal drug
delivery such as simple solutions, lotions, creams, ointments, gels, foams, and aero-
sols due to low enhancement of drug permeation and drug solubility. Over the cen-
turies, several routes have been investigated for the administration of a variety of
medicinal products. The global transdermal drug delivery market system had an
estimated net worth of US $55,100.33 million in 2021 and is projected to reach US
$88,422.40 million by 2030, having a compound annual growth rate of 5.0% from
2021 to 2030 (Phatale etal. 2022). However, their transport through these routes is
constrained by the anatomy of the skin and physiological characteristics of cells.
The skin’s topmost layer, the stratum corneum (SC), serves as the primary barrier to
drugs passing through the skin. It is composed of corneocytes or dead skin cells.
Overcoming this barrier is the major challenge faced by researchers in formulating
drugs and tools of drug delivery to the skin (Farjami etal. 2021; Peña-Juárez etal.
2021). A wide range of transdermal systems containing different drugs have been
J. Kaur et al.
271
formulated, but permeation barriers in the skin limit their clinical use (Kováčik
etal. 2020).
Among the different methods for drug delivery to the skin, nano-sized systems
have attracted attention as drug carriers for transdermal drug delivery (Takeuchi
etal. 2019). To facilitate transdermal absorption, diverse methodologies have been
developed and patented (Brown etal. 2006). This has made it essential to create
novel topical and transdermal drug delivery systems, such as nano-based technolo-
gies that signicantly improve dermatotherapy and overcome several formulation
limitations, such as drug solubility (Durga etal. 2022), resolving some of the sub-
sequent complications with oral drug delivery, including the hepatic rst-pass effect,
longer dosing frequencies, and patient compliance (Ramadon et al. 2021). Such
distinctively intact skin structures serve as a useful barrier for the majority of medic-
inal products and foreign compounds. Thus, numerous unique ways have been
developed to design appropriate transdermal drug delivery systems in order to effec-
tively administer biologically active substances via transdermal route. Some of the
common and advanced investigational strategies involve the use of permeation
enhancers, iontophoresis, microneedles (MNs), sonophoresis, laser ablation, ther-
mal ablation, magnetophoresis, jet injectors, electroporation, and nanocarriers to
boost skin permeation of drugs (Phatale etal. 2022). For nanocarriers, they are clas-
sied as polymer-based nanocarriers, lipid-based nanocarriers, viral nanoparticles,
or inorganic nanoparticles, depending on their constituent parts. The most cutting-
edge drug delivery method recently available is the lipid-based nanocarrier system
which provides ease of large-scale production, biocompatibility, and biodegradabil-
ity due to the nature of the materials used, low toxicity, the possibility of controlled
and modied drug release, drug solubility enhancement, and the potential to incor-
porate hydrophilic and lipophilic drugs. The two types of lipid-based nanocarriers
that might be used to carry therapeutics are vesicular and nonvesicular. Vesicular
lipid-based nanocarriers include liposomes, niosomes, ethosomes, cubosomes,
bilosomes, transfersomes, and glycerosomes, and nonvesicular lipid-based nanocar-
riers include solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs),
and nanoemulsions (Priya etal. 2022).
In this book chapter, we will explain about strategies mediated by nanocarriers
that address various transdermal drug delivery challenges, their clinical signi-
cance, and the most recent developments in research on a few of the existing and
potential transdermal delivery technologies and approaches.
11.2 Formulation Challenges ofTopical
andTransdermal Products
There are numerous challenges associated with topical and transdermal products
that are covered in the subsections below.
11 Challenges and Advances in Pharmaceutical Development of Topical…
272
11.2.1 Drug Solubility
Pharmaceutical formulation has been impacted by the solubility of medicines.
Polymeric micelles have gained much interest as an innovative method to overcome
the poor solubility and permeability of drugs across the skin. These are amphiphilic,
biocompatible, and biodegradable copolymer-based self-assembling nanocarriers.
Natural polymers that are frequently utilized include gelatin and albumin, whereas
synthetic polymers include polylactic acid and polyglycolic acid. They are nanocar-
riers that encapsulate hydrophilic, lipophilic, and charged compounds; decrease the
potential for systemic side effects; and facilitate targeted drug delivery (Makhmalzade
and Chavoshy 2018; Yotsumoto etal. 2018). Compared to other nanocarriers, they
are smaller in size and exhibit better stability in different microenvironments
(Ghezzi etal. 2021). Apart from this, ethosomes are nano-vesicular carriers suitable
for poorly soluble drugs shown to increase their drug permeation (Abouhussein
2021; Apolinário etal. 2021).
11.2.2 Drug Stability
To overcome some of the limitations in topical and transdermal drug delivery, nano-
emulsions have been developed to improve penetration, drug stability, and absorp-
tion of active molecules, as well as to achieve controlled release (Sarheed et al.
2020; Souto etal. 2022). Nanoemulsions are lipid-based, colloidal oil in water dis-
persions of nely dispersed droplets (in the nm scale) with hydrophilic and lipo-
philic phases (Klang etal. 2012; Sarheed etal. 2020). They improve both polar and
nonpolar chemical solubility and are disposable. Compared to conventional emul-
sions, they have greater thermodynamic and kinetic stability and an increased bio-
availability of lipophilic compounds from the addition of surfactants/emulsier. The
uidic nature of nanoemulsions and surfactant interface promotes skin interaction.
In addition, they have a high loading capacity of hydrophobic molecules and protect
the active molecules from oxidation and hydrolysis, which improves bioavailability.
Furthermore, a clinical study by Yamada etal. demonstrated enhanced topical drug
delivery of hydrophobic drugs in a tailorable nanoemulsion using elongated mic-
roparticles that could penetrate the dermal-epidermal junction and enhance drug
permeability within the epidermis (Rai etal. 2018; Yamada etal. 2018).
11.2.3 Skin Irritation
Researchers have examined the microneedles (MNs) for drug delivery by the trans-
dermal route as well as addressing the drawbacks of the current techniques. They
have created a rened method utilizing the microneedles in order to allow hydro-
philic high molecular weight chemicals to penetrate the stratum corneum. Skin pos-
sesses a number of defense systems to protect itself from a variety of environmental
challenges. Microneedle usage can result in mild to moderate skin irritation or
J. Kaur et al.
273
allergies among people with sensitive skin. It may cause inammation, discomfort,
and redness sometimes. If the microneedles are not sterile, the holes they create in
the skin can get infected. Even though the pores produced by microneedles are
much smaller than those made by hypodermic needles, they exhibit less microbial
invasion. These limitations are very rare and can be overcome with advanced mate-
rial selection for microneedles (Waghule etal. 2019).
11.2.4 Bioequivalence Assessment andRegulatory Requirements
Bioequivalence is of utmost importance in topical and transdermal products as it
ensures that generic versions of these products are therapeutically equivalent to
their reference (brand-name) counterparts. Bioequivalence refers to the equivalent
systemic exposure of the active pharmaceutical ingredient (API) between two prod-
ucts when administered in the same dosage form and route and under similar condi-
tions. Generic substitution, safety and efcacy, regulatory requirements, formulation
optimization, and post-marketing surveillance are some key reasons why bioequiva-
lence is crucial in topical and transdermal products.
The availability of generic versions of topical and transdermal products can sig-
nicantly reduce healthcare costs. Bioequivalence studies provide the scientic evi-
dence needed to prove that a generic product can be safely and effectively substituted
for the reference product. This facilitates patient access to more affordable treat-
ment options. These studies provide assurance that generic alternatives deliver the
same amount of active ingredient to the systemic circulation as the reference prod-
uct. This ensures that the generic product will produce the same therapeutic effect
and safety prole as the reference product. Patients can condently switch between
the generic and reference products without compromising their treatment outcomes.
Regulatory authorities, such as the US Food and Drug Administration (FDA) and
the European Medicines Agency (EMA), require bioequivalence data for the
approval of generic topical and transdermal products. These agencies have estab-
lished guidelines that specify the acceptable limits of variability in drug release and
absorption proles. Compliance with these guidelines helps manufacturers demon-
strate that their product is comparable to the reference product. These studies can
assist manufacturers in optimizing the formulation of their topical and transdermal
products. Understanding the factors inuencing drug release and absorption, such
as excipient selection, formulation design, and patch or gel structure, enables manu-
facturers to develop products that achieve similar systemic exposure to the reference
product. This helps ensure that the product delivers the desired therapeutic effect.
Moreover, these studies continue to play a crucial role in post-marketing surveil-
lance of generic topical and transdermal products. Ongoing monitoring of generic
products in the market helps identify any potential variations in efcacy or safety.
Bioequivalence studies can be used to compare the performance of different generic
versions and ensure that they maintain the required standards.
11 Challenges and Advances in Pharmaceutical Development of Topical…
274
11.2.5 Challenges inDevelopment ofStandardized
Bioequivalence Studies
Developing standardized bioequivalence protocols for topical and transdermal
products can be a complex and challenging process. These challenges arise due to
the unique characteristics of topical and transdermal delivery systems, which require
specic considerations in designing bioequivalence studies. This paragraph dis-
cusses the major challenges faced in developing standardized bioequivalence proto-
cols for topical and transdermal products.
Topical and transdermal products present unique challenges due to their complex
delivery systems. Topical products can vary in terms of formulation, such as creams,
ointments, gels, or solutions, each with different properties that can affect drug
release and absorption. Meanwhile, transdermal products often comprise drug-
containing patches or lms that adhere to the skin, requiring careful consideration
of factors like patch design, adhesion, and drug release kinetics. Developing stan-
dardized bioequivalence protocols for these diverse delivery systems is challenging,
as the studies need to account for these formulation variations while ensuring accu-
racy and reproducibility. One of the fundamental goals of bioequivalence studies is
to measure drug absorption accurately. However, this becomes challenging with
topical and transdermal products, as it is difcult to assess the extent of drug absorp-
tion within the skin. Unlike oral medications, where measuring drug concentrations
in blood plasma provides a direct reection of systemic exposure, bioavailability
assessment for topical and transdermal products often involves assessing drug levels
within the skin layers, which may require invasive techniques like microdialysis.
Developing standardized protocols that can reliably measure drug absorption in a
noninvasive and reproducible manner is a signicant challenge.
Skin permeability varies among individuals due to factors like age, skin type,
ethnicity, and underlying skin conditions. This variability can signicantly affect
the bioavailability of topically applied drugs, making it challenging to establish
standardized protocols that account for this variation. Developing bioequivalence
protocols that adequately address this variability to ensure accurate comparison of
absorption between reference and generic products is a complex task. Determining
a therapeutic endpoint for topical and transdermal products is another challenge in
developing standardized bioequivalence protocols. Unlike oral medications, where
systemic drug concentrations or pharmacodynamic effects can serve as reliable
therapeutic endpoints, dening an endpoint for topically applied drugs can be more
subjective. For example, in dermatologic conditions, multiple parameters such as
erythema, scaling, or pruritus may need to be considered. Developing consensus on
clinically relevant therapeutic endpoints and incorporating them into standardized
protocols is crucial but challenging. Topical and transdermal products frequently
contain various excipients and formulation differences that can affect drug release
and absorption. These excipients and formulation variables are crucial in ensuring
product stability, skin penetration, and drug efcacy. However, their potential inu-
ence on bioavailability and bioequivalence must be carefully considered and stan-
dardized across different products. Establishing protocols that adequately address
J. Kaur et al.
275
the impact of formulation variances and excipient effects is essential but compli-
cated, as the range of possible formulations is extensive.
Efforts to overcome these challenges involve collaboration among regulatory
authorities, industry experts, and academia to establish standardized bioequivalence
protocols for topical and transdermal products. This includes setting criteria for
study design, selection of appropriate invitro and invivo methods, statistical analy-
sis, and acceptance.
11.2.6 Regulatory Approval Process forTopical andTransdermal
Dosage Forms
The regulatory approval process for topical and transdermal dosage forms involves
several stages to ensure the safety, efcacy, and quality of these products. This pro-
cess is overseen by regulatory authorities such as the US Food and Drug
Administration (FDA) in the United States and the European Medicines Agency
(EMA) in Europe. While the specic requirements may vary for different countries,
the overall process remains similar. Before conducting clinical trials, the preclinical
development stage focuses on evaluating the safety and efcacy of the topical or
transdermal product through laboratory and animal studies. This involves conduct-
ing pharmacokinetic and toxicological studies to determine the absorption, distribu-
tion, metabolism, excretion, and potential adverse effects of the product. These
studies assess the formulation, manufacturing process, stability, and compatibility
of the product with the skin to ensure its integrity and safety. If the preclinical stud-
ies show promising results, an Investigational New Drug (IND) application is sub-
mitted to the regulatory authority. The IND application includes data from preclinical
studies, details of the proposed clinical trials, information on the manufacturing and
control of the product, and any previous human experience if available. The regula-
tory authority reviews the IND application to evaluate the proposed clinical trials
and assess the safety of the product. The clinical trial phase involves conducting
controlled studies in human subjects to assess the safety, efcacy, and bioequiva-
lence of the topical or transdermal product. The clinical trial protocol is developed,
detailing the study design, dosing regimen, inclusion and exclusion criteria, and
endpoints to measure efcacy. The trials typically involve two groups—an experi-
mental group receiving the investigational product and a control group receiving
either a placebo or a reference product. The trials are conducted according to Good
Clinical Practice (GCP) guidelines, ensuring the ethical conduct of the study and
data integrity. Once the clinical trials are complete, the sponsor submits a New Drug
Application (NDA) in the United States or a Marketing Authorization Application
(MAA) in Europe to the regulatory authorities. These applications provide compre-
hensive data on the product, including information on its safety, efcacy, manufac-
turing process, quality control, labeling, and proposed intended use. The regulatory
authority reviews the application and determines whether to grant marketing
approval based on the evaluation of the data. After receiving marketing approval,
the regulatory authority monitors the product’s safety through post-marketing
11 Challenges and Advances in Pharmaceutical Development of Topical…
276
surveillance. This involves ongoing monitoring of adverse events, periodic safety
updates, and compliance with any post-approval commitments. The regulatory
authority may also conduct inspections of manufacturing facilities to ensure contin-
ued quality control and compliance with Good Manufacturing Practice (GMP)
guidelines.
Throughout the regulatory approval process, it is essential to comply with spe-
cic guidelines and regulations for topical and transdermal dosage forms. These
guidelines provide detailed requirements for various aspects of product develop-
ment, including the selection of appropriate study designs, invitro and invivo meth-
ods for bioequivalence assessment, statistical analysis, and acceptance criteria.
Adhering to these guidelines helps ensure standardized protocols and allows for
consistent and reliable assessment of topical and transdermal products.
11.2.7 Challenges inMeeting Regulatory Guidelines
Meeting regulatory guidelines for topical and transdermal products can present
various challenges. Variability in skin permeability, invitro versus invivo correla-
tion, sensitivity to formulation and application factors, interchangeability of patch
products, stability, and shelf life are some key challenges in meeting regulatory
guidelines. The skin is a complex barrier that can vary signicantly across individu-
als and body sites and even within the same individual over time. This variability in
skin permeability poses a challenge in ensuring consistent drug delivery and absorp-
tion across different populations. Manufacturers need to carefully select appropriate
test sites and consider inter- and intra-subject variability when designing bioequiva-
lence studies (Maibach and Wester 2013). In vitro release studies are commonly
employed to assess the equivalence of drug release from topical and transdermal
products. However, establishing a correlation between invitro release and invivo
drug absorption can be challenging. Factors such as skin metabolism, binding to
skin components, and drug degradation within the skin can affect the invivo bio-
availability, which may not be fully predicted by invitro studies. Therefore, manu-
facturers often need to conduct invivo studies to establish bioequivalence (Barry
2012). Topical and transdermal products can be inuenced by various formulation
and application factors, such as the type of vehicle, pH, occlusiveness, and applica-
tion technique. These factors can affect drug release, absorption, and distribution,
resulting in potential differences in bioavailability between the generic and refer-
ence products. Manufacturers need to carefully control these factors to ensure bio-
equivalence (Ghosh et al. 2014). For transdermal patches, ensuring the
interchangeability of adhesive patches can be challenging. Variations in adhesive
properties, such as adhesion strength, peel force, and drug release kinetics, can
impact drug absorption and efcacy. Manufacturers need to validate the inter-
changeability of adhesive patches through comparative bioequivalence studies to
prove that generic versions are therapeutically equivalent to the reference product
(Noel etal. 2017). Stability and shelf life of topical and transdermal products can
impact their efcacy and quality assurance. Changes in active pharmaceutical
J. Kaur et al.
277
ingredient concentration, dissolution, degradation, and physical properties can
affect drug release and absorption. Manufacturers need to conduct stability studies
to demonstrate that the generic product remains stable over time and is bioequiva-
lent to the reference product throughout its stated shelf life (Sawnhey etal. 2016).
By addressing these challenges, manufacturers can ensure that their topical and
transdermal products meet regulatory guidelines for bioequivalence, thereby pro-
viding safe and effective alternatives to the reference products.
11.3 Manufacturing Challenges
Scaling up the manufacturing process of topical and transdermal dosage forms can
be challenging due to several factors. These challenges include formulation issues,
manufacturing process optimization, equipment selection and validation, regulatory
compliance, and quality control.
Developing a formulation that can be scaled up without compromising the prod-
uct’s safety, efcacy, and stability is crucial. Formulation challenges may arise
when transitioning from small-scale laboratory batches to large-scale manufactur-
ing. For example, the viscosity and rheological properties of the formulation may
change, affecting the product’s spreadability and skin adhesion. Formulation adjust-
ments may be required to ensure consistent performance throughout the manufac-
turing process. Scaling up the manufacturing process requires optimizing process
parameters such as mixing, heating, cooling, and drying times to achieve a consis-
tent and reproducible product. The optimization process may involve evaluating
different manufacturing techniques and equipment, identifying critical process
parameters, and conducting process validation studies. Selecting appropriate equip-
ment for large-scale manufacturing is crucial to ensure consistent product quality.
Equipment scale-up considerations include factors such as mixing capacity, heating
and cooling rates, processing times, and the ability to maintain process control
parameters. Equipment validation studies should be conducted to verify that the
equipment performs as intended and consistently produces the desired product.
Regulatory compliance is essential throughout the manufacturing process.
Manufacturing facilities must meet Good Manufacturing Practice (GMP) guide-
lines to ensure the quality, safety, and efcacy of the topical or transdermal product.
The facilities must be designed and maintained to prevent cross-contamination,
ensure proper hygiene, and control environmental factors that can affect product
quality. Adequate documentation and record-keeping are necessary to demonstrate
compliance with regulatory requirements. Quality control plays a crucial role in
ensuring consistent product quality during scale-up. Robust quality control mea-
sures should be in place to monitor critical quality attributes such as drug content,
release rate, and physical properties of the product. Analytical testing methods
should be developed and validated to ensure accurate and reliable results. Quality
control checks should be performed at different stages of the manufacturing process
to identify and address any deviations.
11 Challenges and Advances in Pharmaceutical Development of Topical…
278
For example, let’s consider the scaling up of a transdermal patch for pain man-
agement. In small-scale laboratory batches, the selected formulation effectively
delivers the active ingredient across the skin barrier and provides the desired anal-
gesic effect. However, when scaling up the manufacturing process, challenges may
arise. The viscosity of the formulation may change, affecting the adhesive proper-
ties of the patch and its ability to adhere to the skin consistently. Formulation adjust-
ments may be required to maintain the desired adhesion and drug delivery
characteristics.
Additionally, the manufacturing process optimization may involve evaluating
different mixing techniques, optimizing heating and cooling rates, and ensuring suf-
cient drying times for large-scale production. The equipment used for mixing,
drying, and packaging should be validated to ensure it consistently produces patches
with the desired quality attributes. Regulatory compliance is crucial in the manufac-
turing process of transdermal patches. The manufacturing facility must meet GMP
guidelines to ensure the integrity and quality of the product. Proper documentation
and record-keeping are necessary to demonstrate compliance during regulatory
inspections. Quality control measures play a vital role in ensuring consistent prod-
uct quality.
11.3.1 Ensuring Consistency andReproductivity
intheManufacturing Process
Ensuring consistency and reproducibility in the manufacturing process of topical
and transdermal products is essential to maintain product quality and meet regula-
tory requirements. Here are some key strategies to achieve this:
Establishing a standardized formulation is crucial to ensure consistent product
performance. This includes dening the composition and concentrations of active
ingredients, excipients, and any other components used in the formulation. This
formulation should be thoroughly tested and validated to conrm its stability, ef-
cacy, and safety. Process validation is an essential step in establishing consistency
and reproducibility in manufacturing. It involves designing and executing experi-
ments or trials to demonstrate that the manufacturing process consistently produces
products that meet the predetermined quality standards. This validation process
should assess critical process parameters, equipment performance, and the impact
of variability on product quality. Standard Operating Procedures (SOPs) should be
developed and implemented to guide operators through the manufacturing process.
SOPs should include detailed instructions, specications, and acceptance criteria
for each manufacturing step. Adequate training of personnel is crucial to ensure
they understand and follow the SOPs correctly. Implementing a robust quality con-
trol program is essential to monitor product quality throughout the manufacturing
process. This involves conducting regular testing of both raw materials and nished
products to verify their compliance with specications. Analytical methods used for
testing should be validated to ensure accuracy and reliability.
J. Kaur et al.
279
Implementing a comprehensive quality assurance program is important to over-
see and control all aspects of the manufacturing process. This includes conducting
regular audits, ensuring compliance with GMP guidelines, and maintaining proper
documentation and record-keeping. Quality assurance personnel should regularly
review batch records, test data, and other quality-related documents to identify any
deviations or issues. Implementing controls to ensure batch-to-batch consistency is
crucial. This can include using well-dened and controlled manufacturing pro-
cesses, conducting in-process checks and testing, and implementing robust change
control procedures. Any changes in raw materials, equipment, or manufacturing
procedures should be thoroughly evaluated and validated before implementation.
Regularly evaluating the manufacturing process for opportunities for improvement
is important to achieve consistency and reproducibility. This can involve monitoring
process performance metrics, conducting root cause analysis for any deviations or
failures, and implementing corrective and preventive actions.
By employing these strategies, manufacturers of topical and transdermal prod-
ucts can ensure consistent and reproducible manufacturing processes. This, in turn,
helps to maintain product quality, efcacy, and safety while also meeting regulatory
requirements.
11.4 Advances inPharmaceutical Development
11.4.1 Nanotechnology-Based Drug Delivery System inTopical
andTransdermal Formulations
The latest developments in topical and transdermal drug delivery systems have
made it possible to administer therapies precisely to the site of action by enhancing
drug penetration through the stratum corneum and improving bioavailability. Some
dermatoses currently have few treatment options available despite different techni-
cal advances because of possible side effects and difculties developing formula-
tions. Approximately 16% of an adult’s entire body weight is made up of skin,
which is said to be the body’s biggest organ. As a result, it is important for maintain-
ing homeostasis (Tortora and Derrickson 2018) and functioning as a chemical,
physical, and biological barrier against external environmental hazards (Dehdashtian
etal. 2018). While traditional topical and transdermal formulations such as creams
and ointments are adequate for treating some dermatological diseases, the limita-
tions and drawbacks of bioavailability and targeted drug delivery necessitate the
development and advancement of technologies to improve drug permeation and
increase drug delivery (Das Kurmi etal. 2017).
Other physical penetration strategies in transdermal delivery being researched
are sonophoresis (Nguyen and Banga 2018; Park etal. 2019), iontophoresis (Park
etal. 2019), and electroporation (Baveja 2018). They are usually regarded as secure,
productive, and efcient with good medicine bioavailability. In addition, a novel
method of delivering medicine called electroporation employs tiny impulses of
electricity. This facilitates the passage of hydrophilic drugs into the stratum
11 Challenges and Advances in Pharmaceutical Development of Topical…