Displaying publications 21 - 40 of 48 in total

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  1. Chan HK, Hassali MA, Lim CJ, Saleem F, Ghani NA
    Pharm Pract (Granada), 2016 Apr-Jun;14(2):699.
    PMID: 27382422 DOI: 10.18549/PharmPract.2016.02.699
    BACKGROUND: Inadequacies of drug labeling have been frequently reported among Malaysian healthcare institutes, in which the Hospital Information System (HIS) is used.
    OBJECTIVE: To identify potential areas to improve the existing labels used for pediatric liquid medications.
    METHODS: This study was qualitative in nature, whereby focus group discussions (FGDs), face-to-face interviews (FTFIs), and onsite observation were used for data collection. Pharmacists stationed at three units (outpatient, inpatient and clinical pharmacy) of a tertiary hospital were targeted. Both FGDs and FTFIs were facilitated using a semi-structured interview guide, video-recorded and transcribed verbatim. All transcripts were thematically analyzed using content analysis approach.
    RESULTS: Thirteen pharmacists participated in FGDs, while five were approached for FTFIs. Data analysis resulted in four major themes: format of labels, presentation of medication instructions, insufficiency of information, and the need for external aids and education. Participants unanimously agreed on the need for enlarging font sizes of key information. Suggestions were made to use more specific instructions for administration times and pictograms to illustrate important directions. The absence of information about storage, stability and handling of liquid medications was also highlighted. While discussion mainly focused on improving drug labeling, participants consistently stressed the need for an instruction sheet and pharmacist-based, one-to-one education regarding medication instructions.
    CONCLUSION: This study provides important insights into critical shortcomings in current labeling practice, underlying the need for developing a new label that incorporates a new format, additional information and pictograms for pediatric liquid medications.
    KEYWORDS: Child; Drug labeling; Hospital; Hospital Information Systems; Malaysia; Medication Errors; Pharmacy Service
  2. Hoe CH, Suan MAM, Hoe CH, Tang TH, Kiew KK, Hassan MRA, et al.
    Med J Malaysia, 2018 08;73(4):260.
    PMID: 30121693
    No abstract provided.
  3. Tan KC, Chang CT, Cheah WK, Vinayak CR, Chan HK
    Med J Malaysia, 2019 Jun;74(3):215-218.
    PMID: 31256176
    INTRODUCTION: This study was designed to determine the influence of bariatric surgery on changes in the body mass index (BMI), and the control of diabetes, hypertension and dyslipidaemia among obese patients in Malaysia.

    MATERIALS AND METHODS: This was a retrospective cohort study undertaken at a public tertiary care centre in the state of Perak, Malaysia. Information of obese patients who underwent bariatric surgery was obtained from their medical records. The changes in the BMI, HbA1C, systolic and diastolic blood pressure (SBP and DBP), and lipid levels between three months before and after the surgery were assessed.

    RESULTS: The patients (n=106) were mostly Malay (66.0%), had at least one comorbidity (61.3%), and had a mean age of 40.38±11.75 years. Following surgery, the BMI of the patients was found to reduce by 9.78±5.82kg/m2. For the patients who had diabetes (n=24) and hypertension (n=47), their mean HbA1C, SBP and DBP were also shown to reduce significantly by 2.02±2.13%, 17.19±16.97mmHg, and 11.45±12.63mmHg, respectively. Meanwhile, the mean total cholesterol, triglyceride and low-density lipoprotein levels of those who had dyslipidaemia (n=21) were, respectively, lowered by 0.91±1.18mmol/L, 0.69±1.11mmol/L and 0.47±0.52mmol/L.

    CONCLUSION: The findings suggest that in addition to weight reduction, bariatric surgery is helpful in improving the diabetes, hypertension and dyslipidaemia control among obese patients. However, a large-scale trial with a control group is required to verify our findings.

  4. Soffian SSS, Nawi AM, Hod R, Chan HK, Hassan MRA
    PMID: 34639786 DOI: 10.3390/ijerph181910486
    The increasing pattern of colorectal cancer (CRC) in specific geographic region, compounded by interaction of multifactorial determinants, showed the tendency to cluster. The review aimed to identify and synthesize available evidence on clustering patterns of CRC incidence, specifically related to the associated determinants. Articles were systematically searched from four databases, Scopus, Web of Science, PubMed, and EBSCOHost. The approach for identification of the final articles follows PRISMA guidelines. Selected full-text articles were published between 2016 and 2021 of English language and spatial studies focusing on CRC cluster identification. Articles of systematic reviews, conference proceedings, book chapters, and reports were excluded. Of the final 12 articles, data on the spatial statistics used and associated factors were extracted. Identified factors linked with CRC cluster were further classified into ecology (health care accessibility, urbanicity, dirty streets, tree coverage), biology (age, sex, ethnicity, overweight and obesity, daily consumption of milk and fruit), and social determinants (median income level, smoking status, health cost, employment status, housing violations, and domestic violence). Future spatial studies that incorporate physical environment related to CRC cluster and the potential interaction between the ecology, biology and social determinants are warranted to provide more insights to the complex mechanism of CRC cluster pattern.
  5. Syed Soffian SS, Safian N, Nawi AM, Ahmad SB, Chan HK, Abu Hassan MR
    PLoS One, 2021;16(10):e0258129.
    PMID: 34618854 DOI: 10.1371/journal.pone.0258129
    The uptake of the immunochemical faecal occult blood test (iFOBT) in many countries with an opportunistic colorectal cancer (CRC) screening programme remains suboptimal. This study aimed to determine the rate, associated factors and reasons of refusal to perform the iFOBT test offered under an opportunistic CRC screening programme in semi-urban communities. This cross-sectional study was conducted among the average-risk individuals living in semi-urban areas, who sought care from public primary care centres across Kedah state, Malaysia. The information regarding the sociodemographic and clinical characteristics of individuals who were offered the iFOBT between January and April 2019, along with their willingness to perform the test, was gathered. The factors associated with the refusal were further explored using the logistic regression analysis. The individuals offered the iFOBT (n = 920) were mainly female (52.4%) and had a mean age of 58.7±10.6 years. The refusal rate of the iFOBT was 32.2%. Patients who did not have hypertension (adjusted OR: 3.33; 95% CI: 2.44, 4.54), did not have CRC symptoms (adjusted OR: 3.15; 95% CI:1.26, 7.89), had the test offered by either medical assistants (adjusted OR: 2.44; 95% CI: 1.71, 3.49) or nurses (adjusted OR: 2.41; 95% CI 1.65, 3.51), did not have diabetes (adjusted OR: 1.99; 95% CI: 1.42, 2.77),and were not active smokers (adjusted OR: 1.74; 95% CI: 1.22, 2.47), were more likely to refuse the iFOBT. The common reasons of refusing the test included "feeling not ready for the test" (21.6%) and "feeling healthy" (14.9%). The iFOBT was refused by one-third of the average-risk individuals from semi-urban communities. The associated factors and reasons of refusal found in this study could guide policymakers in developing targeted interventions to boost the uptake of CRC screening in Malaysia.
  6. Mohd Suan MA, Chan HK, Sem XH, Shilton S, Abu Hassan MR
    Med J Malaysia, 2021 Nov;76(6):828-832.
    PMID: 34806668
    INTRODUCTION: A major challenge in providing hepatitis C virus (HCV) treatment at primary healthcare clinics is the lack of radiological facilities to guide the decision making of liver cirrhosis (LC). This study aimed to compare the performance of three commonly used cut-offs of the aspartate aminotransferase-to-platelet ratio index (APRI) in diagnosing LC among hepatitis C patients in Malaysia.

    METHODS: This cross-sectional study was based on the data collected from the Hepatitis C Elimination through Access to Diagnostics (HEAD-Start) study in 25 primary healthcare clinics across three regions of Malaysia. The findings of biochemical tests were used to calculate the APRI for each study participant. Transient elastography was used as a standard reference for the diagnosis of cirrhosis. The area under the receiver operating curve (AUROC) was used to determine the discriminative ability of APRI in both HCV mono-infected and HCV/HIV co-infected patients. The diagnostic performance of APRI at three different cutoffs (>1.0, ≥1.5 and >2.0) were also evaluated.

    RESULTS: This study included 867 HCV-RNA-positive patients, 158 (16.1%) were co-infected with HIV. For the HCV mono-infected patients, the sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) for the cut-off of >1.0 were 61.8%, 88.7%, 73.8% and 81.9%, and for the cut-off of ≥1.5, 45.6%, 97.0%, 88.7% and 77.6%, respectively. A much lower sensitivity (29.9%) was observed for the cut-off of >2.0. The diagnostic accuracy of APRI at the cut-off of ≥1.5 in the HCV/HIV co-infected patients was relatively suboptimal.

    CONCLUSION: APRI, with a cut-off of ≥1.5, can more accurately predict LC among hepatitis C patients in Malaysia. However, additional physical examination and laboratory assessment are likely to be required to support the diagnosis, especially in those with HCV/HIV co-infection.

  7. Chan HK, Soelar SA, Md Ali SM, Ahmad F, Abu Hassan MR
    Asia Pac J Public Health, 2018 03;30(2):137-146.
    PMID: 29292654 DOI: 10.1177/1010539517751312
    The current study examined how the trends in childhood vaccination refusal in Kedah, Malaysia, changed over a 4-year period (2013-2016). Data contributed by 60 public health centers were used to determine the annual incidence rates (per 1000 newborns) of vaccination refusal, and to identify the reasons for refusal among the mothers. The trend analysis revealed a 2.2-times increment in the incidence rates of vaccination refusal from 4.72 in 2013 to 10.51 in 2015, followed by a 52.2% reduction to 5.02 in 2016 ( P = .046). Besides, the proportion of mothers who refused vaccination because of religious belief reduced from 78% between 2013 and 2015 to 67.1% in 2016 ( P = .005). Overall, the finding confirms the positive impact of the educational and religious interventions introduced by the State Health Department of Kedah since January 2016; nonetheless, efforts to strengthen the existing strategies and thereby to maximize the vaccination coverage in Kedah are warranted.
  8. Suan MAM, Chan HK, Sem X, Shilton S, Hassan MRA
    Sci Rep, 2022 Nov 23;12(1):20153.
    PMID: 36418369 DOI: 10.1038/s41598-022-24612-9
    This cross-sectional study evaluated the performance of the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) and the Fibrosis-4 (FIB-4) Index when they were used individually and in sequential combination to diagnose cirrhosis associated with hepatitis C virus infection. The final evaluation involved 906 people living with hepatitis C. The diagnostic performance of individual biomarkers at cut-off scores of 1.5 and 2.0 for the APRI and at 3.25 for the FIB-4 index was assessed. For the sequential combination method, the cirrhosis status of individuals with an APRI score between 1.0 and 1.5 were reassessed using the FIB-4. Transient elastography (TE) was used as the reference standard for diagnosing cirrhosis. The APRI, at a cut-off score of 1.5, showed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 44.9%, 97.6%, 91.1% and 76.3%, respectively. Increasing the cut-off score to 2.0 produced a much lower sensitivity (29.6%) and NPV (71.9%). The FIB-4, at a cut-off score of 3.25, yielded a sensitivity, specificity, PPV and NPV of 40.8%, 97.3%, 89.1% and 75.0%, respectively. The sequential combination method demonstrated a much more optimal diagnostic performance (50.2% sensitivity, 96.6% specificity, 89.0% PPV and 77.9% NPV). Overall, the APRI and FIB-4 Index performed better in diagnosing cirrhosis associated with hepatitis C when they were used in sequential combination.
  9. Sharma M, Chan HK, Lavilla CA, Uy MM, Froemming GRA, Okechukwu PN
    Fundam Clin Pharmacol, 2023 Aug;37(4):769-778.
    PMID: 36905079 DOI: 10.1111/fcp.12892
    Streptozotocin (STZ) is a broad-spectrum antibiotic that is toxic to the insulin-producing beta cells of the pancreatic islets. STZ is currently used clinically for the treatment of metastatic islet cell carcinoma of the pancreas and the induction of diabetes mellitus (DM) in rodents. So far, there has been no previous research to show that STZ injection in rodents causes insulin resistance in type 2 diabetes mellitus (T2DM). The purpose of this study was to determine if rats (Sprague-Dawley) developed type 2 diabetes mellitus (insulin resistance) after 72 h of intraperitoneal administration of 50 mg/kg STZ. Rats with fasting blood glucose levels above 11.0 mM, 72 h post-STZ induction, were used. The body weight and plasma glucose levels were measured every week throughout the 60-day treatment period. The plasma, liver, kidney, pancreas, and smooth muscle cells were harvested for antioxidant, biochemical analysis, histology, and gene expression studies. The results revealed that STZ was able to destroy the pancreatic insulin-producing beta cell, as evidenced by an increase in plasma glucose level, insulin resistance, and oxidative stress. Biochemical investigation indicates that STZ can generate diabetes complications through hepatocellular damage, elevated HbA1c, kidney damage, hyperlipidemia, cardiovascular damage, and impairment of the insulin-signaling pathway.
  10. Mardhiah K, Wan-Arfah N, Naing NN, Hassan MRA, Chan HK
    Medicine (Baltimore), 2021 Jun 25;100(25):e26160.
    PMID: 34160382 DOI: 10.1097/MD.0000000000026160
    Melioidosis is an infectious disease that is initiated by a bacteria recognized as Burkholderia pseudomallei. Despite the high fatality rate from melioidosis, there is a minimal published study about the disease in Malaysia.This study aimed to identify the prognostic factors of mortality among melioidosis patients in northern Malaysia.All inpatient patients who were admitted to Hospital Sultanah Bahiyah, Kedah and Hospital Tuanku Fauziah, Perlis with culture-confirmed melioidosis during the period 2014 to 2017 were included in the study. The study retrospectively collected 510 melioidosis patients from the Melioidosis Registry. Hazard ratio (HR) used in advanced multiple Cox regression was used to obtain the final model of prognostic factors of melioidosis. The analysis was performed using STATA/SE 14.0 for Windows software.From the results, among the admitted patients, 50.1% died at the hospital. The mean age for those who died was 55 years old, and they were mostly male. The most common underlying disease was diabetes mellitus (69.8%), followed by hypertension (32.7%). The majority of cases (86.8%) were bacteremic. The final Cox model identified 5 prognostic factors of mortality among melioidosis patients. The factors were diabetes mellitus, type of melioidosis, platelet count, white blood cell count, and urea value. The results showed that bacteremic melioidosis increased the risk of dying by 3.47 (HR: 3.47, 95% confidence intervals [CI]: 1.67-7.23, P = .001) compared to non-bacteremic melioidosis. Based on the blood investigations, the adjusted HRs from the final model showed that all 3 blood investigations were included as the prognostic factors for the disease (low platelet: HR = 1.76, 95% CI: 1.22-2.54, P = .003; high white blood cell: HR = 1.49, 95% CI 1.06-2.11, P = .023; high urea: HR = 2.92, 95% CI: 1.76-4.85, P 
  11. Halim NAAA, Chang CT, Chan HK, Hassali MA, Nouri A
    Malays J Med Sci, 2018 Nov;25(6):141-147.
    PMID: 30914888 MyJurnal DOI: 10.21315/mjms2018.25.6.15
    The aim of this cross-sectional study was to evaluate the knowledge and attitudes concerning antibiotic use and resistance among members of the local community in Pulau Pinang, Malaysia. The study was conducted among 326 residents of the Jelutong district, Pulau Pinang state, from August to October 2013. A self-administered five-part questionnaire was used for the data collection. The respondents exhibited inadequate knowledge of antibiotics in general. Approximately 80% of them did not know the indications for antibiotic use, while 76% believed that antibiotics were useful in terms of resolving viral fever. Additionally, 52.6% believed that antibiotics could be used to treat all types of infections. Inadequate knowledge of antibiotic resistance was also evident among the respondents, since 72.9% of them did not agree that resistant bacteria can spread from human or animal to human, while 32% were unaware that bacteria can develop resistance to antibiotics. More than 60% of respondents admitted that they took antibiotics in order to accelerate their recovery from illness, while 34.8% claimed that they only stopped taking antibiotics when they felt better. The findings hence indicate that most respondents had poor knowledge and attitudes concerning antibiotic use and resistance, which suggests the need for more community-based educational campaigns designed to improve the public's knowledge and attitudes regarding antibiotics.
    Study site: General public, Jelutong district, Pulau Pinang, Malaysia
  12. Md Said R, Mohd Zain R, Chan HK, Soelar SA, Rusli N, Nasir NH, et al.
    J Viral Hepat, 2020 06;27(6):638-643.
    PMID: 31997563 DOI: 10.1111/jvh.13267
    Approximately 2.5% of the Malaysian population is currently living with hepatitis C virus (HCV) infection. Yet, the public awareness of the disease is limited and under-screening remains a major challenge. With the support of international non-for-profit organizations, the Ministry of Health in Malaysia recently launched a one-week nationwide hepatitis C screening campaign in conjunction with the World Hepatitis Day. For the first time, the rapid diagnostic test (RDT) for HCV screening was introduced in public health institutions. This campaign involved 49 hospitals and 38 health clinics across the country, targeting the adult general population with unknown HCV infection status. Of the 11 382 participants undergoing the RDT, 1.9% were found to be positive for hepatitis C antibody (anti-HCV) and were referred to on-site medical departments or nearby hospitals for confirmatory testing and treatment. Men, the Malay ethnic group, intranasal and injection drug users and ex-prisoners were shown to have higher odds of being positive for anti-HCV. In addition to serving as a model to educate the general population about the disease, this campaign demonstrates the feasibility of decentralizing HCV screening, particularly by promoting the use of RDT, and linking the HCV-infected patients to care in Malaysia.
  13. Lee FY, Wong HS, Chan HK, Mohamed Ali N, Abu Hassan MR, Omar H, et al.
    Pharmacoepidemiol Drug Saf, 2020 12;29(12):1669-1679.
    PMID: 33064335 DOI: 10.1002/pds.5153
    PURPOSE: To determine the incidence, demographic profile, background of reporters, causative agents, severity and clinical outcomes of hepatic adverse drug reaction (ADR) reports in Malaysia using the national ADR reporting database.

    METHODS: The ADR reports recorded between 2000 and 2017 were retrospectively analysed to identify hepatic ADR reports. The trend and characteristics of hepatic ADR cases were described. Multivariate disproportionality analysis of the causative agents was performed to generate signals of hepatic ADRs.

    RESULTS: A total of 2090 hepatic ADRs (1.77% of all ADRs) were reported with mortality rate of 12.7% among cases with known clinical outcomes. The incidence of hepatic ADR reporting in Malaysia increased significantly over 18 years from 0.26 to 9.45 per million population (P 

  14. Chang CT, Lim XJ, Chew CC, Rajan P, Chan HK, Abu Hassan MR, et al.
    Vaccine, 2022 Dec 12;40(52):7515-7519.
    PMID: 36371369 DOI: 10.1016/j.vaccine.2022.10.057
    The recent wave of COVID-19 cases has led to the potential need for booster doses. We surveyed 6,294 people and found that 87.6% reported willingness to take a booster dose, with vaccine efficacy rate being the most common reason cited to accept booster dose. Differences in acceptance rates were noted among those working in non-health related sectors, different ethnic groups as well as those who had taken viral vector vaccines.
  15. Abu Hassan MR, Hj Md Said R, Zainuddin Z, Omar H, Md Ali SM, Aris SA, et al.
    Heliyon, 2023 Jun;9(6):e16652.
    PMID: 37313177 DOI: 10.1016/j.heliyon.2023.e16652
    BACKGROUND AND PURPOSE: and purpose: Non-alcoholic fatty liver disease (NAFLD) is a significant global health concern with limited pharmacotherapy options. This study aimed to evaluate the effectiveness of a standardized extract of Phyllanthus niruri in mild-to-moderate NAFLD.

    MATERIALS AND METHODS: This was a 12-month randomized controlled trial, in which adults with a controlled attenuation parameter (CAP) score >250 dB/m and a fibrosis score <10 kPa were randomly assigned to receive a standardized P. niruri extract at a dose of 3,000 mg daily (n = 112) or a placebo (n = 114). The primary outcomes were changes in CAP score and liver enzyme levels, while the secondary outcomes were changes in other metabolic parameters. The analysis was performed on an intention-to-treat basis.

    RESULTS: After 12 months, there was no significant difference in the change of CAP score between the intervention and control groups (-15.05 ± 36.76 dB/m vs. -14.74 ± 41.08 dB/m; p = 0.869). There was also no significant difference in the changes of liver enzyme levels between the two groups. However, the intervention group showed a significant reduction in fibrosis score, which was not observed in the control group (-0.64 ± 1.66 kPa versus 0.10 ± 1.61 kPa; p = 0.001). No major adverse events were reported in either group.

    CONCLUSION: This study showed that P. niruri did not significantly reduce CAP score and liver enzyme levels in patients with mild-to-moderate NAFLD. However, a significant improvement in fibrosis score was observed. Further research is needed to determine its clinical benefits at different dosages for NAFLD treatment.

  16. Hassan MRA, Chan HK, Nordin M, Yahya R, Sulaiman WRW, Merican SAA, et al.
    Harm Reduct J, 2023 Apr 12;20(1):48.
    PMID: 37046294 DOI: 10.1186/s12954-023-00780-3
    BACKGROUND: Despite advancements in hepatitis C virus (HCV) treatment, low uptake among hard-to-reach populations remains a global issue. The current study aimed to assess the feasibility of a modified same-day test-and-treat model in improving HCV care for people who inject drugs (PWID) living in resource-constrained rural areas.

    METHODS: A pilot study was conducted in four primary healthcare (PHC) centers in Malaysia. The model's key features included on-site HCV ribonucleic acid (RNA) testing using a shared GeneXpert® system; noninvasive biomarkers for cirrhosis diagnosis; and extended care to PWID referred from nearby PHC centers and outreach programs. The feasibility assessment focused on three aspects of the model: demand (i.e., uptake of HCV RNA testing and treatment), implementation (i.e., achievement of each step in the HCV care cascade), and practicality (i.e., ability to identify PWID with HCV and expedite treatment initiation despite resource constraints).

    RESULTS: A total of 199 anti-HCV-positive PWID were recruited. They demonstrated high demand for HCV care, with a 100% uptake of HCV RNA testing and 97.4% uptake of direct-acting antiviral treatment. The rates of HCV RNA positivity (78.4%) and sustained virologic response (92.2%) were comparable to standard practice, indicating the successful implementation of the model. The model was also practical, as it covered non-opioid-substitution-therapy-receiving individuals and enabled same-day treatment in 71.1% of the participants.

    CONCLUSIONS: The modified same-day test-and-treat model is feasible in improving HCV care for rural PWID. The study finding suggests its potential for wider adoption in HCV care for hard-to-reach populations.

  17. Suppan VKL, Tew MM, Wong BC, Chan HK, Chew YW, Tan CS, et al.
    J Orthop Surg (Hong Kong), 2020 3 5;28(1):2309499019895029.
    PMID: 32129141 DOI: 10.1177/2309499019895029
    PURPOSE: A recent 3-month randomized, open-label controlled trial found that the intra-articular hyaluronic acid injection (GO-ON®) given as a single dose of 5 mL is as effective and safe as three repeated doses of 2.5 mL in patients with knee osteoarthritis. However, the information on the long-term efficacy and economic implications of the single-dose regimen is still limited. Hence, this follow-up study was designed to compare the effectiveness and costs of the two regimens 12 months following the treatment.

    METHODS: All the 127 patients, who received either three repeated doses (n = 64) or a single dose (n = 63) of GO-ON in the previous trial, were followed up in month 12 following the treatment. The effectiveness of both the regimens was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the mean WOMAC scores were compared with those recorded at the baseline and in month 3. Additionally, the total treatment costs of the two regimens, taking account of both direct and indirect costs, were computed and compared.

    RESULTS: A total of 125 patients (98.4%) completed the assessment. Despite the reduction of the overall mean WOMAC score from 39.24 to 19.93 (p < 0.001) in the first 3 months following the treatment with GO-ON, no further changes were observed up to month 12 (p > 0.95). In the meantime, the two regimens did not differ in the mean WOMAC scores (p = 0.749) and in the subscale scores for pain (p = 0.970), stiffness (p = 0.526), and physical functioning (p = 0.667) in month 12. The cost for single-dose injection was found to be approximately 30% lower compared to the repeated doses.

    CONCLUSION: These findings indicate that the single larger dose of GO-ON is as effective as the repeated doses over 12 months, and yet the total treatment cost is lowered.

  18. Leung SSY, Parumasivam T, Nguyen A, Gengenbach T, Carter EA, Carrigy NB, et al.
    Eur J Pharm Biopharm, 2018 Jun;127:213-222.
    PMID: 29486303 DOI: 10.1016/j.ejpb.2018.02.033
    This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine. The powders were stored at 4 °C and 20 °C under vacuum. The phage stability and in vitro aerosol performance of the phage powders were examined on the day of production and after 1, 3 and 12 months of storage. A minor titer loss during production was observed for both phages (0.2-0.8 log10 pfu/ml). The storage stability of the produced phage powders was found to be phage and formulation dependent. No further reduction in titer occurred for PEV2 powders stored at 4 °C across the study. The formulation containing 30% leucine maintained the viability of PEV2 at 20 °C, while the formulation containing 40% leucine gradually lost titer over time with a storage reduction of ∼0.9 log10 pfu/ml measured after 12 months. In comparison, the PEV40 phage powders generally had a ∼ 0.5 log10 pfu/ml loss upon storage regardless of temperature. When aerosolized, the total in vitro lung doses of PEV2 were of the order of 107 pfu, except the formulation containing 40% leucine stored at 20 °C which had a lower lung dose. The PEV40 powders also had lung doses of 106-107 pfu. The results demonstrate that spray dried Myoviridae and Podoviridae phage in a simple formulation of leucine and trehalose can be successfully stored for one year at 4 °C and 20 °C with vacuum packaging.
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