PIncompatibility of Paracetamol with Pediatriapers by Prof. Hamzah M Maswadeh
Cetuximab (CTX) is known to have cytotoxic effects on several human cancer cells in vitro; howeve... more Cetuximab (CTX) is known to have cytotoxic effects on several human cancer cells in vitro; however, as CTX is poorly water soluble, there is a need for improved formulations can reach cancer cells at high concentrations with low side effects. We developed (PEG-4000) polymeric nanoparticles (PEGNPs) loaded with CTX and evaluated their in vitro cytotoxicity and anticancer properties against human lung (A549) and breast (MCF-7) cancer cells. CTX-PEGNPs were formulated using the solvent evaporation technique, and their morphological properties were evaluated. Further, the effects of CTX-PEGNPs on cell viability using the MTT assay and perform gene expression analysis, DNA fragmentation measurements, and the comet assay. CTX-PEGNP showed uniformly dispersed NPs of nano-size range (253.7 ± 0.3 nm), and low polydispersity index (0.16) indicating the stability and uniformity of NPs. Further, the zeta potential of the preparations was − 17.0 ± 1.8 mv. DSC and FTIR confirmed the entrapping of CTX in NPs. The results showed IC 50 values of 2.26 μg/mL and 1.83 μg/mL for free CTX and CTX-PEGNPs on the A549 cancer cell line, respectively. Moreover, CTX-PEGNPs had a lower IC 50 of 1.12 μg/mL in MCF-7 cells than that of free CTX (2.28 μg/mL). The expression levels of p21 and stathmin-1 were significantly decreased in both cell lines treated with CTX-PEGNPs compared to CTX alone. The CTX-PEGNPtreated cells also showed increased DNA fragmentation rates in both cancer cell lines compared with CTX alone. The results indicated that CTX-PEGNP was an improved formulation than CTX alone to induce apoptosis and DNA damage and inhibit cell proliferation through the downregulation of P21 and stathmin-1 expression.
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Scientific Reports, 2020
There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is repor... more There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through GIT.
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The main objective of this work was to use the Differential Scanning Calorimetry (DSC) and FTIR s... more The main objective of this work was to use the Differential Scanning Calorimetry (DSC) and FTIR spectroscopy to study the possible drug-drug or drug-excipient (s) interaction in case of concomitant oral administration of paracetamol with the most common used antibiotics for children. Amoxicillin, azithromycin, ce-furoxime axetil and their commercially available suspensions, Amoxil ® , Azith-romax ® and Zinnat ® were used. DSC curves for paracetamol, pure antibiotics, commercially available antibiotics and all binary mixtures used in this study showed drug-drug or drug-excipient (s) physical interaction and indicated a possible chemical interaction. To confirm chemical drug-drug or drug-excipient (s) interaction additional ATR-IR spectra for all samples used in this study were obtained. Results obtained from ATR-IR spectra showed drug-excipient (s) interaction in Zinnat ® , Azithromax ® and binary mixture Azithromax ®-paracetamol, while chemical drug-drug interaction was not observed. From this study it can be concluded that the concomitant oral administration of paracetamol with commercially available antibiotics used in this study is not recommended and duration of two hours between the oral administrations of these drugs is strongly recommended to avoid drug-drug or drug-excipient (s) interaction.
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CONCOMITANT ORAL ADMINISTRATION OF IBUPROFEN AND SOME COMMONLY USED ANTIBIOTICS FOR CHILDREN: COMPATIBILITY STUDY USING DSC AND FTIR, 2017
Abstract: The main objective of this work was to use the Differential Scanning Calorimetry (DSC) ... more Abstract: The main objective of this work was to use the Differential Scanning Calorimetry (DSC) and FTIR
spectroscopy to study the possible drug-drug or drug-excipient(s) interaction in case of concomitant oral administration
of ibuprofen with the most common used antibiotics for children. Amoxicillin, azithromycin, cefuroxime
axetil and their commercially available suspensions, AmoxilÆ, AzithromaxÆ and ZinnatÆ were used. DSC
curves for ibuprofen, pure antibiotics, commercially available antibiotics and all binary mixtures used in this
study showed drug-drug or drug-excipient(s) interaction and indicate a possible chemical interaction. To confirm
chemical drug-drug or drug-excipient(s) interaction additional ATR-IR spectra for all samples used in this
study were obtained. Chemical interaction in solid state (drug-drug interaction) was observed by FTIR between
cefuroxime axetil and ibuprofen in the binary mixture cefuroxime axetil / ibuprofen (1 : 1, w/w). Also a chemical
interaction in solid state (drug-excipients interaction) was observed in ZinnatÆ suspension (between
cefuroxime and excipients), AzithromaxÆ suspension (between azithromycin and excipients) and mixture of
AzithromaxÆ-ibuprofen (between ibuprofen and excipients). From this study it can be concluded that the concomitant
oral administration of ibuprofen with commercially available antibiotics used in this study in not recommended
and duration of two hours between the oral administrations of these drugs is strongly recommended
to avoid drug-drug or drug-excipient(s) interaction.
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Objectives: Liposomes are reported as penetration enhancers for dermal and transdermal delivery. ... more Objectives: Liposomes are reported as penetration enhancers for dermal and transdermal delivery. However, little is known about their percutaneous penetration and as to at which level they deliver encapsulated drugs. The penetration of multilamellar vesicles (MLVs) and small unilamellar vesicles (SUVs), in comparison to one of their lipid components, was investigated. Methods: Using the fluorescent lipid, Lissamine Rhodamine B-PE (R), as a constituent, MLV and SUV liposomes were prepared, tested, and R, MLV, or SUV were applied in vivo on the back of hairless mice. Absorption of each was evaluated at the levels of stratum corneum, living skin, and blood by fluorometry. Results: Penetration of the lipid R in stratum corneum in the nonliposomal form exceeded that in the liposomal form and only R penetrates the living skin in a statistically significant manner. No statistical significant absorption into blood was observed with either form. Conclusions: Liposomes size did not play an important role in penetration to stratum corneum. The lipid constituent in the nonliposomal form penetrated at higher rates into stratum corneum and living skin. Even though these liposomes entered stratum corneum, they were not significantly absorbed into viable skin or blood.
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The goal of this study was to investigate the physical quality control parameters of dietary supp... more The goal of this study was to investigate the physical quality control parameters of dietary supplements tablets commercially available on the Kingdom of Saudi Arabia by using weight variation, friability and disintegration tests. The impact of immersion medium pH and the use of disk during disintegration test of dietary supplements as well as a price comparison with respect to quality were investigated. All products were found to fulfill the USP <2091> weight variation and <1216> friability tests of dietary supplements. Results for disintegration test by using phosphate buffer or distilled water without disk showed that nine of seventeen tablets did not disintegrate within 30 minutes. Wile by using 0.1 HCl pH = 1.1 without disk 6 of seventeen tablets did not disintegrate. In all disintegration tests with different immersion medium in which disk has been used, only one of seventeen tablets did not disintegrate. The results of the disintegration study indicated that pH of immersion medium as well as the use of disk in the observation cylinder has an important impact on the ability of products to pass the disintegration test. Price comparison showed that product with higher price is not necessary to be the best. Some products with low price were shown rapid disintegration in different pH and they have higher number of tablets, vitamins and minerals in each container than other more expensive products that did not pass the disintegration test. Industrial relevance: Content uniformity requirement for drug product is an acknowledgment of the existence of a well-defined dose-response curve and, thus, dosing intervals, such a requirement is not possible for multivitamin-mineral combination products used as nutritional supplements. Alternatively, weight variation, friability and disintegration tests could be used to ensure that the product was indeed manufactured under good manufacturing practices. Introduction The quantitative evaluation and assessment of a tablet's chemical, physical and bioavailability properties are important in the design of tablets and to monitor product quality. These properties are important since chemical breakdown or interactions between tablet components may alter the physical tablet properties, and greatly affect the bioavailability of the tablet system. There are various standards that have been set in the various pharmacopoeias regarding the quality of pharmaceutical tablets. These include the diameter, size, shape, thickness, weight, hardness, friability, disintegration and dissolution characters. The diameters and shape depends on the die and punches selected for the compression of tablets. The remaining specifications assure that tablets do not vary from one production lot to another (Lachman L et al, 1987). To ensure that the manufacturers control the variation in the weight of dosage units such as tablets, capsules, and solids in single-unit containers, the drug content of each unit in a lot should be distributed in a narrow range around the label strength. For this purpose, there are two tests, the content uniformity test and an alternative simplified test, the weight variation test. Weight variation test based on a comparison of the weight of the individual tablets (x i) of a sample of tablets with an upper and lower percentage limit of the observed sample average (mean).
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Objective: The main objective of this work was to study the lyoequvailency, dissolution kinetic a... more Objective: The main objective of this work was to study the lyoequvailency, dissolution kinetic and drug – excipient compatibility of commercially available acetaminophen tablets. Methodology: In vitro dissolution studies were carried out using a dissolution apparatus USP (Paddle type) at a paddle speed of 50 rpm. Differential Scanning Calorimetry (DSC) and FTIR spectroscopy were used to study the possibility of drug–excipient interaction. Results: The dissolution data for all products of acetaminophen used in this study were fit to the firstorder equation with a linear regression coefficient of determination r 2 values between 0.886 and 0.977. Also results showed that the best equation that fit to the dissolution data and describe the mechanism of drug release was the Weibull distribution function for Panadol ® , Tylenol and Adol ® , while the dissolution data for Actifast ® was best fit to the Higuchi equation. The dissimilarity factor showed that Actifast ® was non lyoequivalent with the other three products. Differential scanning calorimetry (DSC) curve for Actifast ® showed an interaction of acetaminophen with some excipient(s) present in the product; this interaction was indicated by the decrease of the melting peak of acetaminophen from 170.5 o C to 166.5 o C. Acetaminophen–excipient(s) interaction observed in the DSC curves for Actifast ® was also confirmed from the FTIR spectra. Conclusion: It can be concluded that beneficial drug–excipient interaction was observed in Actifast ® due to the presence of polyethylene glycol (Macrogol) produced an increase in the dissolution rate of Actifast ® in comparison with Tylenol ® , Adol ® and Panadol ® .
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Biochimica et Biophysica Acta (BBA) - Biomembranes, 2004
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The main objective of this study was to prepare controlled release microspheres of ciprofloxacin
... more The main objective of this study was to prepare controlled release microspheres of ciprofloxacin
hydrochloride (Cip-HCl) by using cellulose acetate butyrate (CAB) as a coating polymer and to
study the dissolution kinetics as well as the antimicrobial activity of prepared microspheres. Drugpolymer
ratios were selected to be 1:2 and 1:3. The prepared microspheres were evaluated for
their yield (%), drug entrapping efficiency (%), morphology, X-ray diffractometry (XRD), differential
scanning calorimetry (DSC), in-vitro drug release as well as antibacterial activity. Results and
Discussion Results from scanning electron microscopy (SEM) show spherical shape with relatively
rough surfaces of prepared microspheres. Moreover, results obtained from X-ray diffractometry
(XRD) and differential scanning calorimetry (DSC) analysis indicate the absence of drug—polymer
interaction. The dissolution kinetics and the antibacterial activity of the formulated microspheres
were also investigated. All the prepared formulations show zero order release pattern with a linear
regression coefficient of determination r 2 between 0.96 and 0.99. Also, a linear relationship was
obtained with r 2 0.89 to 0.98 for Higuchi equation, indicating that the release process from prepared
microspheres is diffusion–controlled. The evaluation of antibacterial potential of prepared microspheres
in comparison with standard free Cip-HCl solution shows that the encapsulation of Cip-HCl
in form of microspheres enhanced the antibacterial activity of the drug against both Gram positive
(Streptococcus faecalis and Staphylococcus aureus) and Gram negative bacteria (Pseudomonas
aeruginosa and Escherichia coli) as indicated by the inhibition zones’ diameters supported by the
statistical analysis.
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Objective The main objective of this work was to study the
dissolution kinetics of poorly water-s... more Objective The main objective of this work was to study the
dissolution kinetics of poorly water-soluble drugs, indomethacin
and ibuprofen, from formulated capsules or interactive
mixtures containing fine lactose (FL), as ternary additive, and
coarse lactose as carrier compared with selected commercially
indomethacin capsules and to investigate the role of FL-drug
size ratio on the dissolution.
Results and Discussion It was found that the addition of FL in
lactose-indomethacin capsules enhanced the dissolution of indomethacin
while it has decreased the dissolution of ibuprofen from
the lactose-ibuprofen mixtures. The particle size distributions for
drugs and fine lactose used in this study suggested that the
difference in dissolution behaviour for the two drugs could be
due to the FL-drug ratio. Results obtained from the application of
different dissolution kinetic equations showed that the first-order
equation can best describe the kinetic of the dissolution for
Rothacin®, Indylon®, Indomin® and ternary-formulated capsules
of indomethacin, while the dissolution from the binary-formulated
indomethacin capsules showed that the dissolution cannot be
described by zero-order or first-order equations. For ibuprofen
mixtures, the results showed that the release followed the firstorder
kinetic for both systems, binary and ternary mixtures.
Results obtained from Peppas equation showed that all indomethacin
formulations used in this study released the drug by Fickian
release with release exponent (n) <0.45, while all ibuprofen
formulations used in this study released the drug by non-Fickian
(anomalous) release with release exponent (n) >0.45 and >0.89.
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Abstract The main objective of this work was to use the
differential scanning calorimetry in conj... more Abstract The main objective of this work was to use the
differential scanning calorimetry in conjunction with optical
microscopy to study the compatibility of ibuprofen
with lactose and polyvinylpyrrolidone and to provide an
explanation(s) for the reduction in the dissolution rate observed
from the ternary interactive mixture containing
ibuprofen in previous study. Mixtures containing micronized
ibuprofen–fine lactose 90:10 and 20:80 w/w
showed a decrease in the melting peak of lactose by 14.33
and 10.94 C, respectively. The addition of 5 % fine lactose
to the binary system has the highest effect on the
melting point of ibuprofen by reducing the melting peak of
ibuprofen from 76.2 to 73.72 C. Microphotographs obtained
from optical microscopy for ibuprofen, binary and
ternary interactive mixtures showed that agglomeration of
ibuprofen was formed in the binary and ternary interactive
mixtures. Lactose and polyvinylpyrrolidone must be
avoided in the preparation of ternary interactive mixtures
of ibuprofen to prevent drug–excipient interaction.
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Abstract: Small unilamellar vesicles from camel milk phospholipids (CML) mixture or from 1,2 dipa... more Abstract: Small unilamellar vesicles from camel milk phospholipids (CML) mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were prepared, and anticancer drugs doxorubicin (Dox) or etoposide (ETP) were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98%) in liposomes (Lip) prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip.
Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP)-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP). Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).
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Papers by Prof. Hamzah M Maswadeh
Dissolution Technologies, 2022
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Indian Journal of Pharmaceutical Sciences, 2006
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PIncompatibility of Paracetamol with Pediatriapers by Prof. Hamzah M Maswadeh
spectroscopy to study the possible drug-drug or drug-excipient(s) interaction in case of concomitant oral administration
of ibuprofen with the most common used antibiotics for children. Amoxicillin, azithromycin, cefuroxime
axetil and their commercially available suspensions, AmoxilÆ, AzithromaxÆ and ZinnatÆ were used. DSC
curves for ibuprofen, pure antibiotics, commercially available antibiotics and all binary mixtures used in this
study showed drug-drug or drug-excipient(s) interaction and indicate a possible chemical interaction. To confirm
chemical drug-drug or drug-excipient(s) interaction additional ATR-IR spectra for all samples used in this
study were obtained. Chemical interaction in solid state (drug-drug interaction) was observed by FTIR between
cefuroxime axetil and ibuprofen in the binary mixture cefuroxime axetil / ibuprofen (1 : 1, w/w). Also a chemical
interaction in solid state (drug-excipients interaction) was observed in ZinnatÆ suspension (between
cefuroxime and excipients), AzithromaxÆ suspension (between azithromycin and excipients) and mixture of
AzithromaxÆ-ibuprofen (between ibuprofen and excipients). From this study it can be concluded that the concomitant
oral administration of ibuprofen with commercially available antibiotics used in this study in not recommended
and duration of two hours between the oral administrations of these drugs is strongly recommended
to avoid drug-drug or drug-excipient(s) interaction.
hydrochloride (Cip-HCl) by using cellulose acetate butyrate (CAB) as a coating polymer and to
study the dissolution kinetics as well as the antimicrobial activity of prepared microspheres. Drugpolymer
ratios were selected to be 1:2 and 1:3. The prepared microspheres were evaluated for
their yield (%), drug entrapping efficiency (%), morphology, X-ray diffractometry (XRD), differential
scanning calorimetry (DSC), in-vitro drug release as well as antibacterial activity. Results and
Discussion Results from scanning electron microscopy (SEM) show spherical shape with relatively
rough surfaces of prepared microspheres. Moreover, results obtained from X-ray diffractometry
(XRD) and differential scanning calorimetry (DSC) analysis indicate the absence of drug—polymer
interaction. The dissolution kinetics and the antibacterial activity of the formulated microspheres
were also investigated. All the prepared formulations show zero order release pattern with a linear
regression coefficient of determination r 2 between 0.96 and 0.99. Also, a linear relationship was
obtained with r 2 0.89 to 0.98 for Higuchi equation, indicating that the release process from prepared
microspheres is diffusion–controlled. The evaluation of antibacterial potential of prepared microspheres
in comparison with standard free Cip-HCl solution shows that the encapsulation of Cip-HCl
in form of microspheres enhanced the antibacterial activity of the drug against both Gram positive
(Streptococcus faecalis and Staphylococcus aureus) and Gram negative bacteria (Pseudomonas
aeruginosa and Escherichia coli) as indicated by the inhibition zones’ diameters supported by the
statistical analysis.
dissolution kinetics of poorly water-soluble drugs, indomethacin
and ibuprofen, from formulated capsules or interactive
mixtures containing fine lactose (FL), as ternary additive, and
coarse lactose as carrier compared with selected commercially
indomethacin capsules and to investigate the role of FL-drug
size ratio on the dissolution.
Results and Discussion It was found that the addition of FL in
lactose-indomethacin capsules enhanced the dissolution of indomethacin
while it has decreased the dissolution of ibuprofen from
the lactose-ibuprofen mixtures. The particle size distributions for
drugs and fine lactose used in this study suggested that the
difference in dissolution behaviour for the two drugs could be
due to the FL-drug ratio. Results obtained from the application of
different dissolution kinetic equations showed that the first-order
equation can best describe the kinetic of the dissolution for
Rothacin®, Indylon®, Indomin® and ternary-formulated capsules
of indomethacin, while the dissolution from the binary-formulated
indomethacin capsules showed that the dissolution cannot be
described by zero-order or first-order equations. For ibuprofen
mixtures, the results showed that the release followed the firstorder
kinetic for both systems, binary and ternary mixtures.
Results obtained from Peppas equation showed that all indomethacin
formulations used in this study released the drug by Fickian
release with release exponent (n) <0.45, while all ibuprofen
formulations used in this study released the drug by non-Fickian
(anomalous) release with release exponent (n) >0.45 and >0.89.
differential scanning calorimetry in conjunction with optical
microscopy to study the compatibility of ibuprofen
with lactose and polyvinylpyrrolidone and to provide an
explanation(s) for the reduction in the dissolution rate observed
from the ternary interactive mixture containing
ibuprofen in previous study. Mixtures containing micronized
ibuprofen–fine lactose 90:10 and 20:80 w/w
showed a decrease in the melting peak of lactose by 14.33
and 10.94 C, respectively. The addition of 5 % fine lactose
to the binary system has the highest effect on the
melting point of ibuprofen by reducing the melting peak of
ibuprofen from 76.2 to 73.72 C. Microphotographs obtained
from optical microscopy for ibuprofen, binary and
ternary interactive mixtures showed that agglomeration of
ibuprofen was formed in the binary and ternary interactive
mixtures. Lactose and polyvinylpyrrolidone must be
avoided in the preparation of ternary interactive mixtures
of ibuprofen to prevent drug–excipient interaction.
Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP)-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP). Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).
Papers by Prof. Hamzah M Maswadeh
spectroscopy to study the possible drug-drug or drug-excipient(s) interaction in case of concomitant oral administration
of ibuprofen with the most common used antibiotics for children. Amoxicillin, azithromycin, cefuroxime
axetil and their commercially available suspensions, AmoxilÆ, AzithromaxÆ and ZinnatÆ were used. DSC
curves for ibuprofen, pure antibiotics, commercially available antibiotics and all binary mixtures used in this
study showed drug-drug or drug-excipient(s) interaction and indicate a possible chemical interaction. To confirm
chemical drug-drug or drug-excipient(s) interaction additional ATR-IR spectra for all samples used in this
study were obtained. Chemical interaction in solid state (drug-drug interaction) was observed by FTIR between
cefuroxime axetil and ibuprofen in the binary mixture cefuroxime axetil / ibuprofen (1 : 1, w/w). Also a chemical
interaction in solid state (drug-excipients interaction) was observed in ZinnatÆ suspension (between
cefuroxime and excipients), AzithromaxÆ suspension (between azithromycin and excipients) and mixture of
AzithromaxÆ-ibuprofen (between ibuprofen and excipients). From this study it can be concluded that the concomitant
oral administration of ibuprofen with commercially available antibiotics used in this study in not recommended
and duration of two hours between the oral administrations of these drugs is strongly recommended
to avoid drug-drug or drug-excipient(s) interaction.
hydrochloride (Cip-HCl) by using cellulose acetate butyrate (CAB) as a coating polymer and to
study the dissolution kinetics as well as the antimicrobial activity of prepared microspheres. Drugpolymer
ratios were selected to be 1:2 and 1:3. The prepared microspheres were evaluated for
their yield (%), drug entrapping efficiency (%), morphology, X-ray diffractometry (XRD), differential
scanning calorimetry (DSC), in-vitro drug release as well as antibacterial activity. Results and
Discussion Results from scanning electron microscopy (SEM) show spherical shape with relatively
rough surfaces of prepared microspheres. Moreover, results obtained from X-ray diffractometry
(XRD) and differential scanning calorimetry (DSC) analysis indicate the absence of drug—polymer
interaction. The dissolution kinetics and the antibacterial activity of the formulated microspheres
were also investigated. All the prepared formulations show zero order release pattern with a linear
regression coefficient of determination r 2 between 0.96 and 0.99. Also, a linear relationship was
obtained with r 2 0.89 to 0.98 for Higuchi equation, indicating that the release process from prepared
microspheres is diffusion–controlled. The evaluation of antibacterial potential of prepared microspheres
in comparison with standard free Cip-HCl solution shows that the encapsulation of Cip-HCl
in form of microspheres enhanced the antibacterial activity of the drug against both Gram positive
(Streptococcus faecalis and Staphylococcus aureus) and Gram negative bacteria (Pseudomonas
aeruginosa and Escherichia coli) as indicated by the inhibition zones’ diameters supported by the
statistical analysis.
dissolution kinetics of poorly water-soluble drugs, indomethacin
and ibuprofen, from formulated capsules or interactive
mixtures containing fine lactose (FL), as ternary additive, and
coarse lactose as carrier compared with selected commercially
indomethacin capsules and to investigate the role of FL-drug
size ratio on the dissolution.
Results and Discussion It was found that the addition of FL in
lactose-indomethacin capsules enhanced the dissolution of indomethacin
while it has decreased the dissolution of ibuprofen from
the lactose-ibuprofen mixtures. The particle size distributions for
drugs and fine lactose used in this study suggested that the
difference in dissolution behaviour for the two drugs could be
due to the FL-drug ratio. Results obtained from the application of
different dissolution kinetic equations showed that the first-order
equation can best describe the kinetic of the dissolution for
Rothacin®, Indylon®, Indomin® and ternary-formulated capsules
of indomethacin, while the dissolution from the binary-formulated
indomethacin capsules showed that the dissolution cannot be
described by zero-order or first-order equations. For ibuprofen
mixtures, the results showed that the release followed the firstorder
kinetic for both systems, binary and ternary mixtures.
Results obtained from Peppas equation showed that all indomethacin
formulations used in this study released the drug by Fickian
release with release exponent (n) <0.45, while all ibuprofen
formulations used in this study released the drug by non-Fickian
(anomalous) release with release exponent (n) >0.45 and >0.89.
differential scanning calorimetry in conjunction with optical
microscopy to study the compatibility of ibuprofen
with lactose and polyvinylpyrrolidone and to provide an
explanation(s) for the reduction in the dissolution rate observed
from the ternary interactive mixture containing
ibuprofen in previous study. Mixtures containing micronized
ibuprofen–fine lactose 90:10 and 20:80 w/w
showed a decrease in the melting peak of lactose by 14.33
and 10.94 C, respectively. The addition of 5 % fine lactose
to the binary system has the highest effect on the
melting point of ibuprofen by reducing the melting peak of
ibuprofen from 76.2 to 73.72 C. Microphotographs obtained
from optical microscopy for ibuprofen, binary and
ternary interactive mixtures showed that agglomeration of
ibuprofen was formed in the binary and ternary interactive
mixtures. Lactose and polyvinylpyrrolidone must be
avoided in the preparation of ternary interactive mixtures
of ibuprofen to prevent drug–excipient interaction.
Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP)-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP). Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).
Thymoquinone (TQ), a phytoconstituent of Nigella sativa seeds, has been studied extensively in various cancer models. However, TQ’s limited water solubility restricts its therapeutic applicability. Our work aims to prepare the novel formulation of TQ and assess its chemopreventive potential in chemically induced lung cancer animal model.
Methods
The polyethylene glycol coated DOPE/CHEMS incorporating TQ-loaded pH-sensitive liposomes (TQPSL) were prepared and characterized. Mice were exposed to benzo[a]pyrene (BaP) thrice a week for 4 weeks to induce lung cancer. TQPSL was administered three times a week for 21 weeks, starting 2 weeks before the first dose of BaP.
Results
The prepared TQPSL revealed 85% entrapment efficiency with 128 nm size and −19.5 mv ζ-potential showing high stability of the formulation. The pretreatment of TQPSL showed the recovery in BaP-modulated relative organ weight of lungs, cancer marker enzymes, and antioxidant enzymes in the serum. The histopathological analysis of the tissues showed that TQPSL protected the malignancy in the lungs. The flow cytometry data revealed the induction of apoptosis and decreased intracellular ROS by TQPSL. Molecular docking was performed to predict the TQ’s affinity for eight possible anticancer drug targets linked to lung cancer etiology. The data assisted to identify the serine/threonine-protein kinase BRAF as the most suitable target of TQ with binding energy −6.8 kcal/mol.
Conclusion
The current findings demonstrated the potential of TQPSL and its possible therapeutic targets of lung cancer. To our knowledge, this is the first research to outline the development of TQ formulation against lung cancer considering its low solubility as well as pulmonary delivery challenges.
control parameters may differ across various brands. The aim of the present study wasto evaluate
and compare critical quality attributes, including in-vitro dissolution characteristics, of five
acetaminophen tablet brands (labeled A–E) from the Saudi market and determine their
pharmaceutical equivalence. All brands were tested for conformity with the United States
Pharmacopoeia (USP) standards, through evaluation of weight variation, hardness, friability,
disintegration, and dissolution. Dissolution profiles were compared using model-dependent and
independent approaches relative to the innovator brand A (Panadol). All tested brands passed
the weight variation and friability tests with deviations of less than 5% from the average weight
and less than 1% weight loss, respectively, with the exception of brand C showing relatively higher
friability (1.13%). All brands displayed variable disintegration times; however, all were compliant
with USP specifications. All studied tablets released less than 80% of the drug within 30 minutes;
however, brands B and C had lower drug release rates, area under the curve (AUC), and
dissolution efficiency (DE) compared with the innovator. Brand E, on the other hand, had a higher
drug release rate, AUC, DE, and mean dissolution time (MDT), and thus was pharmaceutically
inequivalent to the innovator. All tested brands exhibited a non swellable matrix diffusioncontrolled dissolution as assessed by the Korsmeyer-Peppas model of drug-release kinetics. In
conclusion, all acetaminophen brands were able to pass USP specifications to justify
interchangeability. Minor variations in in-vitro dissolution characteristics could reflect inherent
manufacturing compounding differences.