حمد صالح اليامي

مجال
التميز

تميز دراسي و بحثي

البحوث المنشورة

البحث (1):

عنوان البحث:

Evidence-Based   Nanoscopic and Molecular Framework   for Excipient
Functionality in Compressed Orally   Disintegrating Tablets

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تاريخ النشر:

 15/07/2014

موجز عن البحث:

The work investigates the adhesive/cohesive
molecular and physical interactions together with nanoscopic features of
commonly used orally disintegrating tablet (ODT) excipients microcrystalline
cellulose (MCC) and D-mannitol. This helps to elucidate the underlying
physico-chemical and mechanical mechanisms responsible for powder
densification and optimum product functionality. Atomic force microscopy
(AFM) contact mode analysis was performed to measure nano-adhesion forces and
surface energies between excipient-drug particles (6-10 different particles
per each pair). Moreover, surface topography images (100 nm2–10 mm2) and
roughness data were acquired from AFM tapping mode. AFM data were related to
ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal
analysis using DSC and TGA, disintegration testing, Heckel and tabletability
profiles. The study results showed a good association between the adhesive
molecular and hysical forces of paired particles and the resultant
densification mechanisms responsible for mechanical strength of tablets. MCC
micro roughness was 3 times that of D-mannitol which explains the high
hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between
MCC particles could not be established from both AFM and FTIR solid state
investigation. On the contrary, D-mannitol produced fragile ODTs due to
fragmentation of surface crystallites during compression attained from its
weak crystal structure. Furthermore, AFM analysis has shown the presence of
extensive micro fibril structures inhabiting nano pores which further
supports the use of MCC as a disintegrant. Overall, excipients (and model
drugs) showed mechanistic behaviour on the nano/micro scale that could be
related to the functionality of materials on the macro scale.

البحث (2):

عنوان البحث:

A Systematic
Investigation of D-Mannitol Functionality in the Development of
Age-Appropriate Formulations

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تاريخ النشر:

10/10/2013

موجز عن البحث:

Advances in the field of oral solid
dosage forms have seen the introduction of technologies specifically aimed
for drug delivery of candidates to children and elderly individuals.1 The
main hurdle being faced with these target patient populations is the
difficulty of swallowing solid bulky dosage forms. This obstacle has led to the development of orally
disintegrating tablets (ODTs) and recently to the influx of various
methodologies to manufacture them, including the cost-effective direct
compression method. Preliminary powder flow characterization of D-mannitol
(particle size distribution 37–50 mm) was carried out using a static angle of
repose test. This was followed by assessment of the mechanical properties of
ODTs by measuring the hardness of compacts
of D-mannitol (99.5%, w/w) with 0.5% (w/w).

البحث (3):

عنوان البحث:

Microparticle
surface layering through dry coating: impact of moisture content and process
parameters on the properties of orally disintegrating tablets

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تاريخ النشر:

26/07/2016

موجز عن البحث:

Objectives:  The
aim of this study was to investigate the influence of process parameters
during dry coating on particle and dosage form properties upon varying the
surface adsorbed moisture of microcrystalline cellulose (MCC), a model
filler/binder for orally disintegrating tablets (ODTs).

Methods: The moisture content of MCC was optimised
using the spray water method and analysed using thermogravimetric analysis.
Microproperty/macroproperty assessment was investigated using atomic force
microscopy, nanoindentation, scanning electron microscopy, tablet hardness
and disintegration testing.

Key findings: The results showed that MCC demonstrated
its best flowability at a moisture content of 11.2% w/w when compared to
control, comprising of 3.9% w/w moisture. The use of the composite powder
coating process (without air) resulted in up to 80% increase in tablet
hardness, when compared to the control. The study also demonstrated that
surface adsorbed moisture can be displaced upon addition of excipients during
dry processing circumventing the need for particle drying before tabletting.

Conclusions: It was concluded that MCC with a
moisture content of 11% w/w provides a good balance between powder
flowability and favourable ODT characteristics.

البحث (4):

عنوان البحث:

Dosage
form preference consultation study in children and young adults: paving the
way for patient-centred and patient-informed dosage form development

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تاريخ النشر:

02/09/2016

موجز عن البحث:

Objectives: The current study aims to evaluate dosage
form preferences in children and young adults together with identifying the
key pragmatic dosage form characteristics that would enable appropriate formulation
of orally disintegrating tablets (ODTs).

Methods: International, multisite, cross-sectional
questionnaire of children and young adults aged from 6 to 18 years.
Eligibility was based on age, ability to communicate and previous experience
in taking medications. The study was carried out at three locations: the UK,
Saudi Arabia and Jordan. The questionnaire instrument was designed for
participant self-completion under supervision of the study team.

Results: 104 questionnaires were completed by the study
cohort (n=120, response rate 87%). Results showed that ODTs were the most
preferred oral dosage forms (58%) followed by liquids (20%), tablets (12%)
and capsules (11%). The preferred colours were pink or white while the
preferred size was small (<8 mm) with a round shape. With regard to
flavour, strawberry was the most preferred (30.8%), while orange was the
least preferred (5.8%). The results also showed that the most important
physical characteristics of ODTs were disintegration time followed by taste,
size and flavour, respectively.

Conclusions: The results of our study support the
WHO’s claim for a shift of paradigm from liquid towards ODTs dosage forms for
drug administration to young children older than 6 years. Data from this
study will also equip formulators to prioritise development of key
physical/performance attributes within the delivery system.

المؤتمرات العلمية:

المؤتمر (1):

عنوان المؤتمر:

Saudi Students Conference (SSC2014)

تاريخ الإنعقاد:

1-2/02/2014

مكان
الإنعقاد:

Scotland
– Edinburgh – UK

طبيعة المشاركة:

Poster

عنوان المشاركة:

Formulation
and process development  of  oral disintegrating tablets (ODTs) –
systematic investigation into the role of Microcrystalline cellulose (MCC)
using direct compression

 ملخص المشاركة:

The
last decade, has brought increased demand for oral disintegrating tablets
(ODTs), and the field has become a fast growing area in the pharmaceutical
industry because of the problem of dysphagia in paediatric and geriatric patients.

The aim
of this study was to formulate ODT with low disintegrating time by using
different concentrations of microcrystalline cellulose (MCC). The main
objective of this study was to investigate the feasibility of incorporating
therapeutic doses of active drugs, such as, theophylline and ibuprofen, in
ODTs based on MCC and mannitol as diluents at various compression pressures.
The hardness, friability, and disintegration time, tablet index, and
porosity, for each ratio was determined. Weight, diameter, thickness, volume,
bulk density and true density were determined as well. Data groups were
compared using one- way analysis of variance (ANOVA) and the significant
differences were determined. It was found that at 2 tonnes pressure the
tablet index (TI) was highest, as the higher the value of tablet index, the
higher the hardness and lower is disintegration time. Results obtained from
preparation of MCC (2%, 5%, 10%, 15%, and 30%), mannitol and 0.5% magnesium
stearate showed that at 30% MCC, tablet index was highest with 15.7 seconds
disintegration time and 94 Newton hardness. The next stage of the
experimental set- up was to investigate the feasibility of delivering
therapeutic doses of ibuprofen (insoluble drug) and theophylline (water
soluble drug). The results showed that optimum formulation of ibuprofen ODT
at a dose of 200 mg was achieved at 1.5 tonnes in the presence of 30% MCC. It
was also found that 200 mg of theophylline at 50% MCC at 2 tonnes was the
most efficient ODT formulation. Based on experimental data, it was evident
that concentration of MCC plays a major role in the formulation of ODTs.

المؤتمر (2):

عنوان المؤتمر:

42^nd CRS
Annual Meeting and Exposition

تاريخ الإنعقاد:

26-29/07/2015

مكان
الإنعقاد:

Edinburgh,
UK

طبيعة المشاركة:

Paper
presentation

عنوان المشاركة:

International
Acceptability Study of Orally Disintegrating Tablets (ODTs) in Children and
Yong Adults

ملخص المشاركة:

Following
the European Regulation for paediatric formulations, the demand for the
production of paediatric dosage forms has escalated. Managing the clinical
needs of children is challenging, especially as this must often be
accomplished using adult medicine formulations.

The
current study aims to evaluate dosage form preferences in children and young
adults along with assessing the key pragmatic dosage form characteristics
that would enable formulation of patient centered orally disintegrating
tablets.

INTRODUCTION:

Paediatric
drug administration is one area of the medical field that has gained
significant attention over the last five to seven years. Pharmacists and
other healthcare professionals in the drug manufacturing industry face a
myriad of difficulties with regard to administration of drugs to young
people.

The
main challenge facing drug manufacturing and production is the appropriate
choice of the dosage forms for drug administration to these target population
[1]. For this reason, the common trend has been the manipulation of adult
dosage forms into a form that can be administered to children. The European
Regulation on medicinal products stipulates that all formulations produced
for young people should be in line with safety measures and should generally
be acceptable to the target population [2].

The
authors in this publication designed the current study with two key
objectives central to the study: evaluation and understanding dosage form
preferences among children and young adults who have a history of taking
medicines and secondly extracting data on key dosage form performance
parameters in the manufacture of orally disintegrating tablets. The study was
conducted in three regions (UK, Saudi Arabia and Jordan) at five different
centers. These included Birmingham children hospital, Nottingham children
hospital (UK), Najran maternity and children hospital, General Thar hospital
(Saudi Arabia) and Specialty hospital in Jordan.

EXPERIMENTAL
METHODS:

This
study was a multi-centre; randomized, open (non- blinded) cross-over study of
children and young adults between the ages of 6-18 years. Eligibility was
based on age, ability to communicate and previous experience in taking
medications.

The
survey instrument was designed for participant self-completion under
supervision of the study team. The study was created in MS Word and included
demographics and oral dosage form preferences. Questionnaires were completed
following a short, non-promotional, demonstration of ODTs.

The
questionnaire consisted of four sections. The first section gathered
information regarding demographic and educational data including gender, age,
and education. The second section comprised of a set of questions regarding
children experience of taking medicines and their preferences for various
dosage forms. The third section of the questionnaire contained questions
regarding physical characteristics such as, preference for color, shape,
size, thickness, taste, and flavor and disintegration time of tablets. In the
last section of the questionnaire, children were asked about their feedback
on the questionnaire.

RESULTS
AND DISCUSSION:

One
hundred and four questionnaires out of one hundred and twenty were completed
over three different countries.

The
table below (table 1) gives the demographic characteristics of the
participants. It gives the breakdown of their gender, age and educational
level. The table also sheds more light on the P value for the different
characteristics. The demographic characteristics were used to calculate the P
value.

Table1. Demographic characteristics of participants

In our
study,the chart below shows the preferred oral dosage forms among the
paediatric population. It indicated that ODTs were the most popular oral
dosage forms (58%) followed by liquids (19%), tablets (12%) and capsules
(11%). On the other hand, study by 
Ibrahim  (2010) showed that the
capsules were the most prefered oral solid dosage forms when compared to
tablets, caplets and soft gel[3].

Figure1.
Distribution of the preferred oral dosage forms among pediatrics in all
regions

The
results obtained for the analysis of the physical characteristics of ODTs
showed that quarter of the participants (25.0%) rated the duration for tablet
disintegration in the mouth as the most important characteristic followed by
the taste (24.05%), size (15.71%), and flavor (13.78%) respectively as shown
in figure 2.

Figure2.
Distribution of the most preferred     
characters of ODTs for All regions

Findings
from this study propose that the formulation of ODTs and their physical
characteristics are of high importance in encouraging patients to continue
using a particular medicine. Additionally, they are important factors in
influencing initial selection of products available in the market especially
with OTC medications.

CONCLUSION:

The
general feeling was that orally disintegrating tablets are a pragmatic dosage
forms for children and young adults. The benefits that accrue to this dosage
form include safety, higher compliance, dose accuracy, stability and ease of
swallowing. Within the pediatric population, orally disintegrating tablets
are more convenient because they combine the advantages of both solid and
liquid dosage forms but without incorporating their disadvantages such as
difficulty in swallowing and lack of stability respectively. From the results
in the current study, it can be concluded that the most preferred colors were
pink and white, the most preferred size is the small sized tablets and the
most preferred shape was round. Similarly, physical characteristics with
regard to the acceptability of ODTs included disintegration time, taste, size
and flavor.

المؤتمر (3):

عنوان المؤتمر:

9th Saudi Students’ Conference

تاريخ الإنعقاد:

13-14/02/2016

مكان
الإنعقاد:

Birmingham, UK

طبيعة المشاركة:

Poster presentation

عنوان المشاركة:

Global Consultation Study of Orally Dissolving
Tablets (ODTs) in Paediatric Population

ملخص المشاركة:

Following
the European Regulation for paediatric formulations, the demand for the
production of paediatric dosage forms has escalated. Managing the clinical
needs of children is challenging, especially as this must often be
accomplished using adult medicine formulations.

The
current study aims to evaluate dosage form preferences in children and young
adults along with assessing the key pragmatic dosage form characteristics
that would enable formulation of patient centered orally disintegrating
tablets.

INTRODUCTION:

Paediatric
drug administration is one area of the medical field that has gained
significant attention over the last five to seven years. Pharmacists and
other healthcare professionals in the drug manufacturing industry face a
myriad of difficulties with regard to administration of drugs to young
people.

The
main challenge facing drug manufacturing and production is the appropriate
choice of the dosage forms for drug administration to these target population
[1]. For this reason, the common trend has been the manipulation of adult
dosage forms into a form that can be administered to children. The European
Regulation on medicinal products stipulates that all formulations produced
for young people should be in line with safety measures and should generally
be acceptable to the target population [2].

The
authors in this publication designed the current study with two key
objectives central to the study: evaluation and understanding dosage form
preferences among children and young adults who have a history of taking
medicines and secondly extracting data on key dosage form performance
parameters in the manufacture of orally disintegrating tablets. The study was
conducted in three regions (UK, Saudi Arabia and Jordan) at five different
centers. These included Birmingham children hospital, Nottingham children
hospital (UK), Najran maternity and children hospital, General Thar hospital
(Saudi Arabia) and Specialty hospital in Jordan.

EXPERIMENTAL
METHODS:

This
study was a multi-center; randomized, open (non- blinded) cross-over study of
children and young adults between the ages of 6-18 years. Eligibility was
based on age, ability to communicate and previous experience in taking
medications.

The
survey instrument was designed for participant self-completion under
supervision of the study team. The study was created in MS Word and included
demographics and oral dosage form preferences. Questionnaires were completed
following a short, non-promotional, demonstration of ODTs.

The
questionnaire consisted of four sections. The first section gathered
information regarding demographic and educational data including gender, age,
and education. The second section comprised of a set of questions regarding
children experience of taking medicines and their preferences for various
dosage forms. The third section of the questionnaire contained questions
regarding physical characteristics such as, preference for color, shape,
size, thickness, taste, and flavor and disintegration time of tablets. In the
last section of the questionnaire, children were asked about their feedback
on the questionnaire.

RESULTS AND DISCUSSION:

One
hundred and four questionnaires out of one hundred and twenty were completed
over three different countries.

The
table below (table 1) gives the demographic characteristics of the
participants. It gives the breakdown of their gender, age and educational
level. The table also sheds more light on the P value for the different
characteristics. The demographic characteristics were used to calculate the P
value.

Table1. Demographic characteristics of
participants

In our
study ,the chart below shows the preferred oral dosage forms among the
paediatric population. It indicated that ODTs were the most popular oral
dosage forms (58%) followed by liquids (19%), tablets (12%) and capsules
(11%). On the other hand, study by 
Ibrahim  (2010) showed that the
capsules were the most preferred oral solid dosage forms when compared to
tablets, caplets and soft gel[3].

The
results obtained for the analysis of the physical characteristics of ODTs
showed that quarter of the participants (25.0%) rated the duration for tablet
disintegration in the mouth as the most important characteristic followed by
the taste (24.05%), size (15.71%), and flavor (13.78%) respectively as shown
in figure 1.

Figure1.
Distribution of the most preferred     
characters of ODTs for All regions

Findings
from this study propose that the formulation of ODTs and their physical
characteristics are of high importance in encouraging patients to continue
using a particular medicine. Additionally, they are important factors in influencing
initial selection of products available in the market especially with OTC
medications.

CONCLUSION:

The general feeling was that orally
disintegrating tablets are a pragmatic dosage forms for children and young
adults. The benefits that accrue to this dosage form include safety, higher
compliance, dose accuracy, stability and ease of swallowing. Within the
paediatric population, orally disintegrating tablets are more convenient
because they combine the advantages of both solid and liquid dosage forms but
without incorporating their disadvantages such as difficulty in swallowing
and lack of stability respectively. From the results in the current study, it
can be concluded that the most preferred colors were pink and white, the most
preferred size is the small sized tablets and the most preferred shape was
round. Similarly, physical characteristics with regard to the acceptability
of ODTs included disintegration time, taste, size and flavor.

المؤتمر (4):

عنوان المؤتمر:

2016 UKICRS
Symposium

تاريخ الإنعقاد:

21-22/04/2016

مكان
الإنعقاد:

Cardiff, UK

طبيعة المشاركة:

Poster presentation

عنوان المشاركة:

Formulation and process development of pediatric
ODTs: A systematic investigation into the role of moisture content on  micro/macro properties of pharmaceutical
excipients

ملخص المشاركة:

Background: The amount
of water related with solids may meaningfully affect physical and mechanical
properties of pharmaceutical materials. Properties such as powder flow,
powder coating, AFM, nanoindntaion, compaction, hardness, friability,
disintegration time are influenced by moisture content. This study aims to
examine the effect of moisture sorption of Micro Crystalline Cellulose (MCC)
on powder blending/coating using a prototype dry powder coater and consequent
tableting by direct compression.

Methods: The moisture
content of MCC was optimized using spray water approach and analysed using
thermogravimetric analysis (TGA). Selected particle sizes of both mannitol
(guest particle size ≤ 38 μm) and MCC (carrier particle size ≥ 250 μm) were
obtained by sieving and confirmed by particle size analyzer. Two different
blends of the mixture of MCC and mannitol were studied: interactive mixtures
obtained by blending the mix at 300rpm for 5 minutes and particle coated mix
obtained by blending at 1500 rpm either with or without air flow.  Consequential ODTs of powder blend
(interactive mixture) and powder coating (with and without air) were
investigated for hardness, friability, disintegration time and porosity.

Results: The results
showed that as moisture content of MCC increases, the flow properties improve
dramatically. MCC demonstrated its best flowability at moisture content of
11.2%, (low angle of repose 29.6±0.86) when compared to control comprising of
3.9% moisture (angle of repose 38.52±0.67). This difference in flow could
possibly be attributed to the lubricant activity of moisture that reduces the
friction between particles and the solid surface. The next sets of
investigations were focused at developing interactive and dry particle coated
(mannitol coated on to MCC) mixtures of MCC with different moisture content
(3.9% and 11.2%).  The results showed
that formation of interactive mixtures resulted in a drop of moisture content
from 3.9% to 1.6and from 11.2% to 2.6 Similarly, upon dry coating without air
the moisture content dropped from 3.9% to 1.7 and from 11.2% to 4.12
Interestingly, inclusion of air flow within the process of dry coating
reduced the moisture content from 3.95 to1.7 and 11.2% to 1.5 These
differences in moisture content of the powder blends, due to variations in
processing conditions demonstrated significant variations in ODT properties.
Stronger compacts were obtained from interactive mixtures for the two
different levels of moisture content for MCC whereas dry coated powder blends
(with and without air) yielded weaker ODTs. These differences in ODT
properties are due to the differences in the moisture content which cements
the particles and impacts on mechanical properties as well as particle
layering with mannitol coated MCC presenting fragment able surfaces which
result in weaker tablets.

Conclusions: Moisture considerably affects the consolidation characteristics of blended
powder. The extent of consolidation and the bonding of particles not
exclusively on moisture content but also on the powder processing conditions.