Name: Hunsa devi

Pharm.D 2nd year (4th semseter)

Ziauddin University
Topic : “ Oral Dosage forms”
1. Recent progress in continuous manufacturing of oral solid
dosage forms
Author : V. Vanhoorne, C. Vervaet
Published 20 December 2019
Reference : https://doi.org/10.1016/j.ijpharm.2020.119194

2.An overview on dosage forms and formulation strategies for

vaccines and antibodies oral delivery
Author : Faten Madani, Hassana Hsein, Virginie Busignies & Pierre
Tchoreloff (2020
Reference : 10.1080/10837450.2019.1689402
Published 24 Nov 2019

3. The Role of Functional Excipients in Solid Oral Dosage Forms to

Overcome Poor Drug Dissolution and Bioavailability
Published 25 April 2020
Author : by Jannes van der Merwe, Jan Steenekamp, Dewald Steyn
and Josias Hamman
Reference : https://doi.org/10.3390/pharmaceutics12050393
4.Oral controlled release dosage forms: dissolution versus diffusion
Published 20 April 2020
Author Marvel Bermejo , Barbara Sanchez-Dengra, Marta Gonzalez-
Alvarez & Isabel Gonzalez-Alvarez.
Reference https://doi.org/10.1080/17425247.2020.1750593

5.Oral Dosage Forms with Controlled Gastrointestinal Transit

Published 20 Oct 2008
Author
R. Gröning & G. Heun
Reference https://doi.org/10.3109/03639048409041405
Summary 1.
For decades, batch-wise manufacturing was the standard for production of oral
solid dosage forms (OSD) in the pharmaceutical industry 1
. In contrast, the continuous manufacturing (CM) model has been used
successfully for many years in the automotive, food, consumer and petrochemical
industry to improve manufacturing efficiency and reduce costs 2
· In a batch process, raw materials are charged into a single unit operation after
which the process is run at validated settings until the pre-determined endpoint is
achieved. The material is then discharged from the unit to test the quality of the
intermediate product through off-line, destructive and time-consuming analytical
methods. These intermediates are temporarily stored in the warehouse until all
quality requirements are met and the material can be transferred to the next unit
operation. In contrast, a continuous process uses the ‘one in, one out’ principle
where starting materials are continuously fed into the process, while the finished
products are continuously removed from the process at the same flow rate to
maintain a constant hold-up mass in the system during steady-state processing 3
· A conventional drug product manufacturing process consists of a series of
separate unit operations (e.g. dispensing, blending, high shear granulation, drying,
tableting). In contrast, an integrated CM process integrates all unit operations in a
single production train, without starts or stops in between unit operations (Figure
1). Consequently, assuring the quality of a continuous process requires
continuous monitoring of critical process parameters (CPPs) as well as quality
attributes of raw materials, intermediates and final drug product via
measurements in the process stream using process analytical technology (PAT).
This allows to detect perturbations in real-time and to steer the CPPs through
feedback and feedforward loops in order to keep the process and the critical
quality attributes (CQAs) of the final product within its operational ranges. As raw
materials are directly converted into finished products via an integrated process
train, CM eliminates the need for handling process intermediates and
thus accelerates the cycle time for release.
It is widely recognized that continuous manufacturing of OSDs can offer many
cost and quality related advantages over batch manufacturing. Nevertheless, only
a limited number of drug products are currently approved for continuous
manufacturing. Recent research studies provided in-depth knowledge on
continuous processes and monitoring possibilities via PAT. It is expected that this
research along with currently available integrated manufacturing equipment and
more detailed and harmonized regulatory frameworks will promote adoption of
CM as preferred manufacturing technology for oral solid dosage forms.
Summary 2:
Most of biopharmaceuticals in clinical use today are available in a
solution or suspension form and delivered by invasive routes (i.e.
injection). However, several attempts have been made in order to
develop effective oral formulations of ‘biomolecules’ characterized by a
fragile structure and a low bioavailability. To achieve an efficient
delivery of such molecules by non-parenteral route, in particular, via
the oral route, novel concepts are needed not only to overcome
significant enzymatic and diffusion barriers but also to ensure stability
and biological activity. Vaccines and antibodies have a special interest
as biomolecules because of their high therapeutic efficacy both in
prevention and treatment of several chronic diseases. In this review, we
would like to highlight the trends made in the development of
pharmaceutical forms to deliver these molecules by the oral route.
Hence, we will focus on the description of the different forms
(solutions, suspensions, powders, tablets, micro and nanocarriers …)
available today or under research study, in which product stability and
efficacy are maintained. A special attention will be paid to the
formulation strategies that may include the addition of several
functional excipients and/or adjuvants, aiming to protect, to
functionalize or to modulate their release in the body.
Summary 3:
Many active pharmaceutical ingredients (APIs) exhibit poor solubility
and low dissolution rates in aqueous environments such as the luminal
fluids of the gastrointestinal tract. The oral bioavailability of these
compounds is usually very low as a result of their poor solubility
properties. In order to improve the bioavailability of these poorly
soluble drugs, formulation strategies have been applied as a means to
improve their aqueous solubility and dissolution rates. With respect to
formulation approaches, excipients can be incorporated in the
formulation to assist in the dissolution process of the drug, or
specialized dosage forms can be formulated that improve dissolution
rate through various mechanisms. This paper provides an overview of
selected excipients (e.g., alkalinizing agents, surfactants and sugars)
that can be used in formulations to increase the dissolution rate as well
as specialized dosage forms such as self-emulsifying delivery systems
and formulation techniques such as inclusion complexes and solid
dispersions. These formulation approaches are discussed with available
examples with specific reference to positive outcomes in terms of drug
solubility and bioavailability enhancement.
Keywords: solubility; bioavailability; excipients; dissolution
1. Introduction
Pharmacologically active compounds or drugs (also referred to as active
pharmaceutical ingredients; APIs) are usually not administered to
patients on their own as single compounds, but are formulated into
carefully designed dosage forms. Pharmaceutical dosage forms provide
a platform for repeatable accurate dosing, quality, efficacy, safety,
stability as well as high patient acceptance and compliance . Initially,
dosage forms were made by simply adding pharmacologically inert
substances (also referred to as excipients) to the API to make up the
required volume of an acceptable dosing unit. However, progress in
pharmaceutical technology has led to the selection and production of
excipients that fulfil specific functions, beyond just making up volume,
such as assisting in production of the dosage form and optimizing drug
delivery from novel dosage forms. In fact, the functions of excipients in
dosage forms are related to all the different aspects of the final product
including its manufacturability, the stability of the API, dose uniformity,
effective delivery of the API to the systemic circulation after
administration as well as acceptable organoleptic properties for
maximum compliance by the patient .
Pharmaceutical excipients are usually included in dosage forms in larger
quantities than the API and can make up to about 90% of the total
mass/volume of medicinal products . The International Pharmaceutical
Excipient Council (IPEC) classified pharmaceutical excipients based on
safety data into two classes namely ‘new chemical excipients’ and
‘established excipients’. The latter class is sub-divided into the following
sub-classes: ‘existing chemical excipients’, ‘existing chemical
excipients—first administration to humans’ and ‘new modifications or
combinations of existing excipients’. These different classes of
pharmaceutical excipients have different requirements in terms of
safety evaluation .Awareness of the importance of excipient quality and
safety, especially in pediatric patients, was intensified by the death of
84 children in 2008 due to inclusion of glycerin contaminated with
diethylene glycol in teething powders .Consequently, updates on
regulatory requirements for pharmaceutical excipients are continuously
introduced worldwide to ensure the safety of patients .
The excipient class ‘new chemical excipients’ can be sub-divided into
‘modified excipients’ (i.e., existing excipients that are modified with
respect to purity and/or physical properties such as particle size), ‘co-
processed excipients’ (i.e., two or more existing excipients which are
formulated into a new excipient with physical properties that cannot be
obtained by a simple physical mixture and is produced through
processes such as spray drying) and ‘novel excipients’ (i.e., new
chemical entities used for the first time in a drug product which may
include known excipients that are chemically modified).
Summary 4:
Controlled release can be achieved through several mechanisms, such
as dissolution, diffusion, solvent-activation (as the osmotic pumps) or
chemical-trigger (by hydrolytic or enzymatic reactions). Many marketed
CR products are diffusion or dissolution limited or a combination of
both mechanisms.
In diffusion-limited CR formulations, insoluble polymers are used for
controlling drug delivery and it is quite easy to obtain a zero-order
kinetic, particularly in multiparticulate reservoir types. Diffusion
through swellable hydrophilic polymers is a second alternative used
mainly in matrix systems, easy to manufacture, and generally having a
non-constant release rate.
Dissolution-limited systems are either based on pH differential
dissolution of a coating polymer or in the dissolution/erosion of soluble
polymers. The former alternative performance may be affected by inter
and intra individual variability on intestinal pH profiles. The later may
need additives to render the dissolution pH-independent.
Frequently, CR forms combine dissolution and diffusion release
mechanisms in matrix type forms. In these cases, it is possible to say
that if the drug is highly soluble, diffusion may be more relevant,
peradventure the drug has low solubility, and then, matrix erosion may
be more important.The main physiological factors affecting CR
performance are intestinal fluids pH, volume and composition, physical
forces, and transit times which determine the time of exposure to the
particular segment conditions. Food influence depends on release
mechanism.
Several in vitro dissolution systems in combination with mechanistic
mathematical modeling can be used as development tool for studying
the kinetics of release and for predicting the in vivo behavior of a CR
formulation with the aim of enhancing the probabilities of success in
human clinical trials.
Summary 5:
Manufacture of the dosage forms:
Tablet press: Betema hand-operated press with compression tool for
tablets. Punch diameter 12 mm, flatfaced, facetted (Betema, Berlin,
FRG). The composition of the myristic acid-containing tablet
The tablet consists of two layers, one with the active ingredient (20'mg
riboflavine) and the other with the transit delaying excipient (165 mg
triethanolamine myristate). At first the active ingredient layer was
compressed.
In constructing floating forms’, attempts are made to
achieve the latest possible passage of the dosage form
into the the duodenum without affecting gastric emptying. According
to this control principle, the released and dissolved drug should reach
the upper, absorbing part of the intestine from the stomach in small
amounts, so that a complete and even absorption ensues.
By actively delaying transit, which was the concern of this study , the
aim is to achieve a controlled gastrointestinal passage through the
release of controlling substances from the drug form. Drugs such as
propantheline or physiologically active constituents of foodstuffs, eg
certain fatty acids, could be added in low concentrations as controlling
agents2. The use of physiologically active elements of foodstuffs to
regulate the gastrointestinal transit of drugs was the new development
of the present investigations. The use of transit-controlling dosage
forms is of special interest for those drug substances which are
only absorbed over a limited period from the duodenum
or the upper part of the small intestine. The results of computer
simulations of the effects of transit-delaying measures on the serum
concentration of a drug with a limited duration of absorption from
the gastrointestinal tract are depicted .