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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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corneum (Baveja 2018). Sonophoresis is the application of various ultrasonic wave
frequencies to penetrate the skin’s protective layer and enhance drug diffusion
through the epidermis, hence enhancing medication penetration. Compared to high-
frequency ultrasound, low-frequency ultrasound improves medication penetration
more (Nguyen and Banga 2018; Park etal. 2019), but in iontophoresis molecules
are pushed into the skin using an electric eld (the repelling forces between simi-
larly charged molecules). For the delivery of both charged and uncharged mole-
cules, it delivers quick drug release (Park etal. 2019). However, since the models
are patient-specic, many of these potential solutions suffer challenges with cost
and large-scale applicability; to evaluate the long-term effects of any of the strate-
gies, greater depth of research and clinical trials are thus necessary.
11.4.2 Personalized Medicine Tailoring Topical andTransdermal
Dosage Forms toIndividual Patient Needs
The eld of personalized medicine, which aims to adapt medicines to a specic
individual by taking into account that person’s physiology, drug action, and genetic
prole, has the potential to revolutionize the healthcare industry. The primary tech-
nology driving this paradigm change from traditional “one-size-ts-all” care to per-
sonalized medicine is three-dimensional (3D) printing. A three-dimensional item is
created utilizing different computer software through the process of 3D printing,
one layer at a time. Using 3D printing, it is feasible to create a wide variety of phar-
maceutical dosage forms with different geometries, release proles, and drug com-
bination. Few of the main 3D printing technical platforms being investigated in the
pharmaceutical sector include stereolithography, selective laser sintering, inkjet
printing, fused lament fabrication, binder jetting, and pressure-assisted microsy-
ringe. In the future, this technology might be used in a clinical context where medi-
cations could be given based on patient needs. Creating products from three
dimensions is known as three-dimensional printing, commonly referred to as addi-
tive manufacturing or 3D printing. It involves depositing layers of material on top of
one another to gradually develop a solid structure. It utilizes CAD software to trans-
mit the required signals to a 3D printer, which converts the computerized digital
model into two-dimensional (2D) portions and creates solid layers to generate the
required objects (Vaz and Kumar 2021).
There is great role of technology in personalized medicines. Inkjet printing, in
general, refers to systems that employ pattern-generating tools to digitally direct
and position tiny liquid drops on a substrate. Continuous inkjet printers, as the name
suggests, continuously emit a ne mist of liquid droplets onto a substrate, even
when not explicitly necessary. This process involves introducing a pressure wave
into the ink supply, resulting in vibrations that break up the ink into consistently
sized droplets which are subsequently expelled from the nozzle. This technique has
been utilized for a considerable period of time due to its consistent emission of ink
droplets. While the advantage lies in the continuous creation of droplets, preventing
clogging of the nozzle, it is worth noting that drawbacks such as low resolution and
J. Kaur et al.
281
costly maintenance accompany this printing method (Vaz and Kumar 2021). In a
drop-on-demand inkjet printer, ink droplets are expelled only when necessary. The
printer typically has 100–1000 nozzles, and each nozzle is capable of independently
ejecting droplets onto the substrate. The trigger signal instructs the printhead to
release the droplets precisely where needed. This technology allows for precise con-
trol and efcient use of ink. In a thermal inkjet (TIJ) printer, thermal energy is used
as the trigger to release the ink droplets. Each nozzle in the printhead has a resistor
that heats up when triggered by an electric charge. This rapid heating causes the ink
to vaporize and form a bubble, which propels the droplet out of the nozzle onto the
substrate. The resistor then cools down, allowing the nozzle to be reloaded with ink
for the next droplet. The main disadvantage of thermal inkjet printers is the use of
high temperatures (around 200–300°C), which can potentially degrade thermola-
bile active compounds present in some inks. This limitation needs to be considered
when using thermal inkjet technology for sensitive applications (Vaz and Kumar
2021). In a piezoelectric inkjet printer, a piezoelectric element or actuator is used to
generate pressure and eject the ink droplets. When an electric voltage is applied to
the piezoelectric material, it changes its shape, exerting pressure on the ink reser-
voir. This pressure forces the ink out through the nozzle, forming a droplet onto the
substrate. Once the piezoelectric element returns to its original shape, the nozzle is
reloaded with ink, ready to be triggered again. This offers advantages such as pre-
cise control of ink droplet size and high-quality printing. They can also handle a
wider range of inks compared to thermal inkjet printers. However, they may be
more expensive and have more complex mechanisms (Alomari etal. 2015; Vadodaria
and Mills 2020). The ability to use less volatile and more biocompatible uids while
operating at room temperature is one of this method’s primary advantages (Acosta-
Vélez 2016; Acosta-Vélez and Wu 2016).
11.4.3 Benefits andChallenges ofDeveloping Combination
Therapies inTopical andTransdermal Formulations
Drug distribution via the skin is a fascinating and difcult eld. It has been both an
intriguing or difcult study topic. Modern technological advancements lead to the
transdermal delivery of various types of medications, including traditional hydro-
phobic small molecules, hydrophilic medications, and macromolecules. Because of
its clear advantages over alternative delivery methods, transdermal systems are a
preferred method of medication administration. Patients can administer themselves
conveniently and painlessly through transdermal delivery. Another advantage of
transdermal drug delivery is the ability to provide a sustained release of medication.
This is particularly useful for medications with a short half-life that would require
frequent dosing. By continuously releasing the drug through the skin, transdermal
systems can maintain a constant plasma level of the medication, resulting in more
effective and consistent therapy. Additional benet of transdermal distribution is
bypassing the gastrointestinal tract that may affect the absorption of medications.
The rst-pass effect can be eliminated, making it safer to provide less medication to
11 Challenges and Advances in Pharmaceutical Development of Topical…
282
hepato-compromised patients and reducing the adverse effect. On a monthly cost
basis, transdermal systems are often less expensive than other therapies since
patches are made to administer medications for 1–7days. The ability to give medi-
cations in numerous doses, on-demand, or at a variable rate is another benet of
transdermal administration. This feature enhances the advantages of traditional
patch dosage forms. The market for transdermal products is expanding, which fur-
ther demonstrates the extremely high level of patient acceptance of transdermal
therapies. The market for transdermal medication delivery, which was valued $12.7
billion in 2005, is anticipated to grow to $32 billion by 2015 (Paudel etal. 2010).
11.4.3.1 Case Studies andExamples ofCombination Therapies
ofTransdermal Patches andTopical Drug
Transdermal systems have predominantly focused on the patch dosage form, yet
there are alternative variations such as metered sprays like Evamist
®
, delivering
estradiol, or gel formulations like AndroGel
®
, delivering testosterone, which oper-
ate within the transdermal era. Technically, these newer transdermal gels can be
seen as a resurgence of the nitroglycerin ointment technology that was previously
approved. However, these updated formulations exhibit enhanced sensory proper-
ties and market appeal. Consequently, these technologies present a viable alterna-
tive to patch production, particularly for potent drug compounds, as they are highly
effective and cost-efcient. Furthermore, for the successful distribution of medica-
tion through transdermal patches, stability is a crucial consideration. With the pos-
sibility of patches containing volatile solvents or hygroscopic materials, appropriate
packaging becomes imperative (Paudel etal. 2010).
11.4.4 Continuous Monitoring andControlled Release
inTransdermal Drug Delivery System
The Internet of Things (IoT) plays a crucial role in smart medicine delivery systems
(Fig.11.1) by utilizing advanced technology to monitor and improve the effective-
ness of medicinal therapy. IoT-based drug delivery systems utilize various hard-
ware, sensors, and smart tools to monitor and evaluate a patient’s health parameters
in real time, leading to customized and targeted medicine therapy. These systems
employ devices of different sizes and types, such as wearable and implantable
devices like infusion pumps, smart pens, inhalers, and auto-injectors. However,
there are a number of difculties in developing and implementing IoT-based medi-
cine delivery systems, including condentiality and privacy of the data collected by
these devices, strict regulations and standards, and compatibility and reliabil-
ity issues.
11.4.4.1 Real-Time Monitoring andControl ofDrug Release
IoT-based medication transdermal delivery systems are becoming more common in
the healthcare industry as a result of their ability to improve drug delivery’s preci-
sion, efcacy, and efciency. Different techniques are used in medicine transdermal
J. Kaur et al.
283
delivery system to examine data, make wise judgments, and optimize therapy. In
systems like insulin administration for detecting diabetes, where data is continually
monitored and evaluated to determine right dosage form, closed-loop control algo-
rithms are utilized. Use of pharmacokinetic and pharmacodynamic algorithms can
improve dosage regimes and help in forecasting medication based pharmacokinetic
processes i.e. absorption, distribution, metabolism and excretion. Datasets are ana-
lyzed by automated algorithms to nd patterns or correlations that guide medicine
dose choices and improve treatment results. Effectiveness and safety of drug deliv-
ery systems are improved by these algorithms, which allow for customized dose
recommendation and modications (Raikar etal. 2023). Smart drug delivery sys-
tems have a great deal of promise of increasing medication adherence and reducing
the load of demanding regimens. By utilizing their connection and smooth data
Fig. 11.1 Categories of IoT-based system
11 Challenges and Advances in Pharmaceutical Development of Topical…
284
exchange capabilities, IoT-based systems provide special benets for smart medi-
cine administration. IoT sensors continually monitor medication delivery parame-
ters, patient responses, and ambient conditions with real-time monitoring and data
analytics, enabling quick intervention and improved treatment procedures (Raikar
etal. 2023). Healthcare practitioners may remotely monitor the condition of patients
due to remote access and connection, which makes them especially useful for tele-
medicine and the management of chronic diseases. Improved treatment outcome
and self-management are a result of enhanced patient engagement through mobile
apps and wearables (Saunders etal. 2019). The infrastructure enables integration
with healthcare systems, allowing smart drug delivery systems to adapt to new needs.
11.5 Conclusion andFuture Perspectives
Conclusion of pharmaceutical development of transdermal and topical dosage
forms presents several challenges and has witnessed signicant advances in recent
years. Key challenges include permeation barriers, limited drug load, and poor sta-
bility of active ingredients. However, advancements in technology and formulation
strategies have addressed some of these challenges. One of the notable advances is
the use of novel delivery systems such as nanoparticles, liposome, and micronee-
dles, which increase penetration of the drug through skin and improve their bio-
availability. These systems provide controlled release, increased drug loading
capacity, and improved stability. Furthermore, the development of sophisticated
invitro/in vivo models for evaluation of drug permeation and skin absorption has
facilitated the screening and selection of effective formulations. These models
mimic human skin properties and aid in predicting drug release and permeation
behavior. Another signicant advance is the incorporation of physical and chemical
penetration enhancers, which can disrupt the skin barrier and increase drug perme-
ation. These enhancers include hydrophilic and lipophilic compounds, as well as
techniques such as iontophoresis, sonophoresis, and microneedle-based intradermal
delivery. Moreover, the introduction of solubility-enhancement strategies, such as
cosolvency, complexation, and nano-emulsication, has improved the formulation
of poorly soluble drugs for transdermal and topical delivery. These approaches
enhance dissolution and solubility of the drugs, leading to improved drug release
and permeation. Despite the notable advancements, there are still areas of research
that need to be explored. Future studies should focus on developing novel strategies
to overcome skin permeation barriers, enhance drug loading capacity, and improve
stability of active ingredients. Additionally, the exploration of personalized medi-
cine and the development of custom-made transdermal and topical forms based on
individual patient needs hold immense potential. To conclude, the pharmaceutical
development of transdermal and topical forms has gradually progressed, along with
advancements in drug delivery systems, penetration enhancers, solubility-
enhancement strategies, and sophisticated evaluation models. These advances have
improved the efcacy and optimization of transdermal and topical system. Continued
J. Kaur et al.
285
research in this eld is expected to yield breakthroughs in overcoming the remain-
ing challenges and bringing transformative changes in development of transdermal
and topical delivery system.
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12
Advances inOphthalmic Formulation
Development
RohitBhawale, VaibhaviSrivastava,
andNeeleshKumarMehra
Abstract
Recent advancement in ophthalmic drug delivery is mostly concentrated on med-
ication administering in the form of simple eye drops. Novel, innovative ophthal-
mic dosage forms possess advancement such as sustained release, less dosing
frequency and improved ocular bioavailability and permeability. The present
chapter will give an overview of the recent progress and challenges related to
advanced ophthalmic dosage forms in addition to anatomy of the human eye and
barriers which will be under consideration while developing ophthalmic drug
delivery systems. Application of 3DP (three-dimensional printing) in advance-
ment of ocular delivery systems will also be discussed in detail along with the
evaluation tests and their regulatory considerations.
Keywords
Ophthalmic · Nanomedicine · Liposomes · Nanoparticles · Regulatory
12.1 Introduction
The eye is a complex but essential sensory organ playing a characteristic role in
providing vision to living organisms. The eye is a delicate organ with complex anat-
omy and physiology (Fig.12.1). The eye’s three adjacent tissue layers—the centre
pigmented layer, the inner neurosensory layer and the outermost collagenous
R. Bhawale · V. Srivastava · N. K. Mehra (*)
Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics,
National Institute of Pharmaceutical Education and Research (NIPER), Ministry of Chemical
and Family Welfare, Hyderabad, Telangana, India
e-mail: neelesh@niperhyd.ac.in
290
layer—are anatomically arranged in this order. The two regions of this physically
and physiologically distinct organ that enable vision are (Irsch and Guyton 2009)
the front or anterior segment (which makes up one-third of the eye) including the
cornea, aqueous humour, conjunctiva, ciliary body, lens and iris and (Patel 2013)
the back or posterior segment (which makes up the remaining two-thirds of the eye),
which is made up of the sclera, retina, vitreous humour, choroid and optic nerve
(Fig.12.2).
To protect and keep this immune-privileged organ apart from the systemic circu-
lation, each eye tissue has a unique structure (Cunha-Vaz 1979). In the anterior
region, the collagenous layer that gives mechanical strength is known as the cornea.
It is translucent in nature and oversees the focusing light on the retina. The brous
collagenous posterior portion is opaque in nature, called sclera. The middle layer, or
uvea, contains the ciliary body and iris. Aqueous humour, which is secreted by the
ciliary body’s smooth muscles and serves as both food for the anterior segment’s
avascular tissues and a regulator of intraocular pressure, is also produced by the cili-
ary body. The ciliary body also carries out debris drainage from the cornea and lens.
The intermediate layer in the posterior part is made up of a huge network of capil-
laries known as the vascular choroid, which provides the retina with all its necessary
nutrients. The retina, which is the innermost layer, aids in transmitting light signals
to the brain. The lens refracts light entering the eye and is located between the two
chambers (Kim et al. 2014). The eye, while having a well-dened physiological
structure and makeup, is a very delicate organ that is prone to a number of disorders,
most often uveitis, which encompasses any inammation of the iris, choroid and
ciliary body together known as the uvea (Yellepeddi and Palakurthi 2016). In many
circumstances, uveal inammation affects the posterior section as well.
Fig. 12.1 The anatomy of the human eye
R. Bhawale et al.