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Controlled release compound based on metanilate-layered double hydroxide nanohybrid

Hussein MZ, Nasir NM, Yahaya AH

J Nanosci Nanotechnol, 2008 Nov;8(11):5921-8.
PMID: 19198327

Metanilate-layered double hydroxide nanohybrid compound was synthesized for controlled release purposes through co-precipitation method of the metal cations and organic anion. The effect of various divalent metal cations (M2+), namely Zn2+, Mg2+ and Ca2+ on the formation of metanilate-LDH nanohybrids, in which metanilate anion was intercalated into three different layered double hydroxide (LDH) systems; Zn-Al, Mg-Al and Ca-Al were investigated. The syntheses were carried out with M2+ to Al3+ initial molar ratio, R of 4. The pH of the mother liquor was maintained at pH 7.5 and 10 during the synthesis, and the resulting mixture was aged at around 70 degrees C for about 18 h. The intercalation of metanilate anion into the host was found to be strongly influenced by the M2+ that formed the inorganic metal hydroxide layers. Under our experimental condition, the formation of the nanohybrid materials was found to be more feasible for the Zn-Al than for the other two systems, in which the former showed well-ordered layered organic-inorganic nanohybrid structure with good crystallinity. Intercalation is confirmed by the expansion of the interlayer spacing to about 15-17 A when metanilate was introduced into the interlamellae of Zn-Al LDHs. In addition, CHNS and FTIR analyses also support that metanilate anion has been successfully intercalated into the interlamellae of the inorganic LDH. Apart from M2+, this study also shows that the initial pH of the mother liquor plays an important role in determining the physicochemical properties of the resulting nanohybrids, especially the mole fraction of the Zn2+ substituted by the Al3+ ion in the LDH inorganic sheets which in turn controlled the loading percentage of the organic anion, surface properties and the true density. Preliminary study shows that LDH can be used to host beneficial guests, active agent with controlled release capability of the guests. Generally the overall process is governed by pseudo second order kinetic but for the first 180 min, the release process can be slightly better described by parabolic diffusion than the other models.
Effect of incoming and outgoing exchangeable anions on the release kinetics of phenoxyherbicides nanohybrids

Sarijo SH, Hussein MZ, Yahaya AH, Zainal Z

J Hazard Mater, 2010 Oct 15;182(1-3):563-9.
PMID: 20633986 DOI: 10.1016/j.jhazmat.2010.06.070

The release of chlorophenoxyherbicides agrochemicals, namely 2-chloro- (2CPA), 4-chloro and 2,4,5-trichloro (TCPA) phenoxyacetates from their nanohybrids into various aqueous solutions; carbonate, sulfate and chloride was found to be controlled by pseudo-second order rate expression. The percentage saturated released was found to be anionic-dependent, in the order of carbonate>sulfate>chloride for the release media and 2CPA>4CPA>TCPA for the anionic guests. This study demonstrates that the release of the phenoxyherbicides agrochemicals from the nanohybrid compounds can be tuned by choosing the right combination of exchangeable anions both the incoming and the outgoing anions.
Controlled release of a plant growth regulator, alpha-naphthaleneacetate from the lamella of Zn-Al-layered double hydroxide nanocomposite

bin Hussein MZ, Zainal Z, Yahaya AH, Foo DW

J Control Release, 2002 Aug 21;82(2-3):417-27.
PMID: 12175754

Formation of the so-called organic-inorganic nanohybrid material was exploited for the preparation of a controlled release formulation. The inorganic Zn-Al-layered double hydroxide (LDH) was used as a matrix, hosting an active agent or a guest, alpha-naphthaleneacetate (NAA), a plant growth regulator by self-assembly technique. The reverse process, i.e., the deintercalation or release of the guest, NAA was found to be rapid initially, followed by a more sustained release thereafter and this behavior was dependent on the pH of the release medium, the aqueous solution. The mechanism of release has been interpreted on the basis of the ion-exchange process between the NAA anion intercalated in the lamella host and nitrate or hydroxyl anions in the aqueous solution.
Bacillus cereus as a biotemplating agent for the synthesis of zinc oxide with raspberry- and plate-like structures

Hussein MZ, Azmin WH, Mustafa M, Yahaya AH

J Inorg Biochem, 2009 Aug;103(8):1145-50.
PMID: 19577306 DOI: 10.1016/j.jinorgbio.2009.05.016

Currently the development of green chemistry approach with the use of biomaterial-based activities of microbial cells in the synthesis of various nanostructures has attracted a great attention. In this study, we report on the use of bacterium, Bacillus cereus as a biotemplating agent for the formation of zinc oxide nanoparticles with raspberry- and plate-like structures through a simple thermal decomposition of zinc acetate by maintaining the original pH of the reaction mixtures. Possible mechanism on the formation of the nanostructures is proposed based on the surface chemistry and biochemistry processes involved organic-inorganic interactions between zinc oxide and the microbial cells.
Controlled release formulation of agrochemical pesticide based on 4-(2,4-dichlorophenoxy)butyrate nanohybrid

Hussein MZ, Hashim N, Yahaya AH, Zainal Z

J Nanosci Nanotechnol, 2009 Mar;9(3):2140-7.
PMID: 19435093

Hybridization of beneficial organic guest with inorganic host affords scientists an opportunity to synthesize various combinations of new organic-inorganic nanohybrids with various potential applications, especially for controlled delivery of beneficial agent and storage. A new layered organic-inorganic nanohybrid material containing an agrochemical, 4-(2,4-dichlorophenoxy)butyrate (DPBA) in Zn-Al-layered double hydroxide inorganic interlayer was synthesised by direct and indirect methods. Both methods yielded mesoporous-type, phase pure, well-ordered layered nanohybrids with similar basal spacing of 28.5-28.7 angstroms and organic loading of around 54.3%. Compared to the material prepared by direct method, the ion exchanged product inherited more of the host's properties especially the pore structure and the organic moiety is also more easily released. This shows that the method of preparation plays an important role in determining the resulting physicochemical properties, in particular the release property and therefore can be used as a means to tune up the release property of the beneficial agent.
Synthesis of 4-chlorophenoxyacetate-zinc-aluminium-layered double hydroxide nanocomposite: physico-chemical and controlled release properties

Hussein MZ, Sarijo SH, Yahaya AH, Zainal Z

J Nanosci Nanotechnol, 2007 Aug;7(8):2852-62.
PMID: 17685307

Layered organic-inorganic hybrid nanocomposite material was synthesised using 4-chlorophenoxyacetate (4CPA) as guest anion intercalated into the Zn-Al layered double hydroxide inorganic host by direct co-precipitation method at pH = 7.5 and Zn to Al molar ratio of 4. Both PXRD and FTIR results confirmed that the 4CPA was successfully intercalated into the Zn-AI-LDH interlayer. As a result, a well-ordered nanolayered organic-inorganic hybrid nanocomposite, with the expansion of the basal spacing from 8.9 angstroms in the layered double hydroxide to 20.1 angstroms in the resulting nanocomposite was observed. The FTIR spectrum of the nanocomposite (ZAC) showed that it composed spectral features of Zn-AI-LDH (ZAL) and 4CPA. The nanocomposites synthesized in this work are of mesoporous-type containing 39.8% (w/w) of 4CPA with mole fraction of Al3+ in the inorganic brucite-like layers (xAI) of 0.224. The release studies showed a rapid release of the 4CPA for the first 600 min, and more sustained thereafter. The total amount of 4CPA released from the nanocomposite interlayer into the aqueous solution were 21%, 66%, and 72% in 0.0001, 0.00025, and 0.0005 M sodium carbonate, respectively. In distilled water, about 75, 35, and 57% of 4CPA could be released in 1000 min, when the pH of the release media was set at 3, 6.25, and 12, respectively. In comparison with a structurally similar organic moiety with one more chlorine atom at the 2-position of the aromatic ring, namely 2,4-dichlorophenoxyacetate (24D), the 4CPA showed a slower release rate. The slightly bulkier organic moiety of 24D together with the presence of chlorine atom at the 2-position presumably had contributed to its higher release rate, and it seems that these factors may be exploited for tuning the release rate of intercalated guest anions with similar properties. This study suggests that layered double hydroxide can be used as a carrier for an active agent and the chemical structure of the intercalated moiety can be used to tune the desired release kinetics of the beneficial agent.
Self-assembled nanocomposite of organic-inorganic hybrid: 2,4-dichlorophenoxyacetate in Zn-Al hydrotalcite-like layers

Hussein MZ, Mohd Amin JB, Zainal Z, Yahaya AH

J Nanosci Nanotechnol, 2002 Apr;2(2):143-6.
PMID: 12908300

Hydrotalcite-like inorganic layers of Zn-Al, a host containing an organic moiety, 2,4-dichlorophenoxy-acetate, as a guest, was prepared by the spontaneous self-assembly method from an aqueous solution for the formation of a new layered organic-inorganic hybrid nanocomposite material. In this synthesis, the host- and guest-forming species were simultaneously included in the mother liquor, aged, and separated. Various Zn/Al ratios (R = 2, 3, and 4), concentrations of 2,4-dichlorophenoxyacetic acid (0.03-0.1 M), and pH (7 and 10) were studied to optimize the formation of the layered nancomposite. It was found that the optimum conditions for the formation of the nanocomposite were R = 4, pH 7, and concentration of 2,4-dichlorophenoxyacetic acid = 0.08 M. X-ray diffraction shows that this sample affords a nanolayered structure with a basal spacing of 24.6 A.
Health-Related Quality of Life among Nonprescription Medicine Customers in Malaysia

Shafie AA, Hassali MA, Mohamad Yahaya AH

Value Health Reg Issues, 2013 May;2(1):107-117.
PMID: 29702838 DOI: 10.1016/j.vhri.2013.02.005

OBJECTIVE: To describe the health-related quality of life (HRQOL) among nonprescription medicine customers in Malaysia and the factors that affect it.
METHODS: A nationwide cross-sectional survey was conducted among pharmacy customers in 59 randomly selected community pharmacies in Malaysia. The self-administered questionnaire included the EuroQoL five-dimensional (EQ-5D) questionnaire, the EuroQol visual analogue scale (EQ-VAS), nonprescription medicines purchase, and demographic questions. Data were analyzed by using the multivariate analysis of variance and multiple logistic regressions.
RESULTS: A total of 2729 customers enrolled in this study, with a mean EQ-5D questionnaire score of 0.92±0.15 and a mean EQ-VAS score of 69.92±24.80. Compared with the Malaysian adult population, nonprescription medicine customers have a lower mean EQ-5D questionnaire score (t =-4.49, P<0.01) and EQ-VAS score (t =-25.87, P<0.01). We found that pain/discomfort (25.6%) and anxiety/depression (13.7%) were the major HRQOL problems. Locality, age, ethnicity, household income per month, type of occupation, and type of nonprescription medicine purchased were associated with health status of nonprescription medicine customers (F22,5286 = 2.555; Wilks' lambda = 0.979; P< 0.01).
CONCLUSIONS: The HRQOL of nonprescription medicine customers is lower than that of the general Malaysian population. Lower health status was independently associated with older age, living in rural areas, having low income and education level, and purchasing blood and blood-forming medicines from community pharmacy.
Fulltext Formation and yield of multi-walled carbon nanotubes synthesized via chemical vapour deposition routes using different metal-based catalysts of FeCoNiAl, CoNiAl and FeNiAl-LDH

Hussein MZ, Jaafar AM, Yahaya AH, Masarudin MJ, Zainal Z

Int J Mol Sci, 2014;15(11):20254-65.
PMID: 25380526 DOI: 10.3390/ijms151120254

Multi-walled carbon nanotubes (MWCNTs) were prepared via chemical vapor deposition (CVD) using a series of different catalysts, derived from FeCoNiAl, CoNiAl and FeNiAl layered double hydroxides (LDHs). Catalyst-active particles were obtained by calcination of LDHs at 800 °C for 5 h. Nitrogen and hexane were used as the carrier gas and carbon source respectively, for preparation of MWCNTs using CVD methods at 800 °C. MWCNTs were allowed to grow for 30 min on the catalyst spread on an alumina boat in a quartz tube. The materials were subsequently characterized through X-ray diffraction, Fourier transform infrared spectroscopy, surface area analysis, field emission scanning electron microscopy and transmission electron microscopy. It was determined that size and yield of MWCNTs varied depending on the type of LDH catalyst precursor that is used during synthesis. MWCNTs obtained using CoNiAl-LDH as the catalyst precursor showed smaller diameter and higher yield compared to FeCoNiAl and FeNiAl LDHs.
Fulltext Does educational intervention improve doctors' knowledge and perceptions of generic medicines and their generic prescribing rate? A study from Malaysia

Hassali MA, Wong ZY, Alrasheedy AA, Saleem F, Mohamad Yahaya AH, Aljadhey H

SAGE Open Med, 2014;2:2050312114555722.
PMID: 26770747 DOI: 10.1177/2050312114555722

To investigate the impact of an educational intervention on doctors' knowledge and perceptions towards generic medicines and their generic (international non-proprietary name) prescribing practice.
Fulltext Patterns and predictors of non-prescription medicine use among Malaysian pharmacy patrons: a national cross sectional study

Hassali MA, Mohamad Yahaya AH, Shafie AA, Saleem F, Chua GN, Aljadhey H

PLoS One, 2013;8(4):e59231.
PMID: 23573195 DOI: 10.1371/journal.pone.0059231

The study aims to evaluate the predictors of non-prescription medicine purchasing patterns among pharmacy patrons in Malaysia.
Perspectives of physicians practicing in low and middle income countries towards generic medicines: a narrative review

Hassali MA, Wong ZY, Alrasheedy AA, Saleem F, Mohamad Yahaya AH, Aljadhey H

Health Policy, 2014 Sep;117(3):297-310.
PMID: 25129135 DOI: 10.1016/j.healthpol.2014.07.014

This review was conducted to document published literature related to physicians' knowledge, attitudes, and perceptions of generic medicines in low- and middle-income countries (LMICs) and to compare the findings with high-income countries.
Fulltext Patients' beliefs about generic medicines in Malaysia

Wong ZY, Hassali MA, Alrasheedy AA, Saleem F, Yahaya AH, Aljadhey H

Pharm Pract (Granada), 2014 Oct;12(4):474.
PMID: 25580171

BACKGROUND: Acceptance of generic medicines by patients is an essential factor given that they are the end users of these medicines. In fact, adequate knowledge and positive perceptions are prerequisite to patients' acceptance and use of generic medicines.
OBJECTIVE: To assess the current belief and views of patients about generic medicines in Malaysia.
METHOD: This was a self-administered questionnaire-based study. The study was conducted with patients visiting outpatient pharmacy department at a tertiary care hospital in Malaysia. The Malaysian version of Generic Medicines Scale (GMS) was used. The GMS consists of two subscales: efficacy and similarity of generic medicines to original brand medicines. The efficacy subscale consists of 10 items while the similarity subscale consists of 6 items. The responses to the items were framed as a five-point Likert scale (1=strongly disagree to 5=strongly agree).
RESULTS: A total of 202 out of 300 patients participated in the study, giving a response rate of 67.3%. In this study, only 49% of them (n=99) knew the term 'generic medicine'. Moreover, only 53.5% of the respondents (n=108) believed that the efficacy of generic medicines was the same as original brand medicines. In terms of quality, only 44% of the respondents (n=89) disagreed that generic medicines were of a lower quality. About one third (n=65, 32.2%) believed that generic medicines were cheaper because they were less efficacious. In terms of side effects, 44.5% of the respondents (n=90) believed that generic medicines had the same side effect profile as original brand medicines.
CONCLUSIONS: The study finding showed that almost half of the respondents had negative belief in generic medicines. Similarly, many patients were not aware of the similarities and differences between generic and original brand medicines. Therefore, there is a need to provide patients with adequate information about generic medicines.

Study site: outpatient pharmacy department at a tertiary care hospital in Malaysia
Fulltext A comparison between antibiotic utilisation in public and private community healthcare in Malaysia

Lim AH, Ab Rahman N, Nasarudin SNS, Velvanathan T, Fong MCC, Mohamad Yahaya AH, et al.

BMC Public Health, 2024 Jan 03;24(1):79.
PMID: 38172715 DOI: 10.1186/s12889-023-17579-3

BACKGROUND: There are two parallel systems in Malaysian primary healthcare services: government funded public primary care and privately-owned practices. While there have been several studies evaluating antibiotic utilisation in Malaysian public healthcare, there is a lack of literature on the use of antibiotics in the private sector. There is a dire need to evaluate the more recent performance of public vs. private community healthcare in Malaysia. As such, this study aimed at measuring and comparing the utilisation of antibiotics in the public and private community healthcare sectors of Malaysia in 2018-2021.
METHODS: This study was a retrospective analysis of antibiotic utilisation in Malaysian primary care for the period of 1 January 2018 until 31 December 2021 using the nationwide pharmaceutical procurement and sales data from public and private health sectors. Rates of antibiotic utilisation were reported as Defined Daily Doses per 1000 inhabitants per day (DID) and stratified by antibiotic classes. The secondary analysis included proportions of AWaRe antibiotic category use for each sector and proportion of antibiotic utilisation for both sectors.
RESULTS: The overall national antibiotic utilisation for 2018 was 6.14 DID, increasing slightly to 6.56 DID in 2019, before decreasing to 4.54 DID in 2020 and 4.17 DID in 2021. Private primary care antibiotic utilisation was almost ten times higher than in public primary care in 2021. The public sector had fewer (four) antibiotic molecules constituting 90% of the total antibiotic utilisation as compared to the private sector (eight). Use of Access antibiotics in the public sector was consistently above 90%, while use of Access category antibiotics by the private sector ranged from 64.2 to 68.3%. Although use of Watch antibiotics in the private sector decreased over the years, the use of Reserve and 'Not Recommended' antibiotics increased slightly over the years.
CONCLUSION: Antibiotic consumption in the private community healthcare sector in Malaysia is much higher than in the public sector. These findings highlight the need for more rigorous interventions targeting both private prescribers and the public with improvement strategies focusing on reducing inappropriate and unnecessary prescribing.

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