In Vitro In Vivo Extrapolation and Bioequivalence Prediction for Immediate-Release Capsules of Cefadroxil Based on a Physiologically-Based Pharmacokinetic ACAT Model.

Physiologically based pharmacokinetic (PBPK) modeling is a mechanistic concept, which helps to judge the effects of biopharmceutical properties of drug product such as in vitro dissolution on its pharmacokinetic and in vivo performance. With the application of virtual bioequivalence (VBE) study, the drug product development using model-based approach can help in evaluating the possibility of extending BCS-based biowaiver. Therefore, the current study was intended to develop PBPK model as well as in vitro in vivo extrapolation (IVIVE) for BCS class III drug i.e. cefadroxil. A PBPK model was created in GastroPlus™ 9.8.3 utilizing clinical data of immediate-release cefadroxil formulations. By the examination of simulated and observed plasma drug concentration profiles, the predictability of the proposed model was assessed for the prediction errors. Furthermore, mechanistic deconvolution was used to create IVIVE, and the plasma drug concentration profiles and pharmacokinetic parameters were predicted for different virtual formulations with variable cefadroxil in vitro release. Virtual bioequivalence study was also executed to assess the bioequivalence of the generic verses the reference drug product (Duricef®). The developed PBPK model satisfactorily predicted Cmax and AUC0-t after cefadroxil single and multiple oral dose administrations, with all individual prediction errors within the limits except in a few cases. Second order polynomial correlation function obtained accurately predict in vivo drug release and plasma concentration profile of cefadroxil test and reference (Duricef®) formulation. The VBE study also proved test formulation bioequivalent to reference formulation and the statistical analysis on pharmacokinetic parameters reported 90% confidence interval for Cmax and AUC0-t in the FDA acceptable limits. The analysis found that a validated and verified PBPK model with a mechanistic background is as a suitable approach to accelerate generic drug development.

A mechanistic study on the inhibition of bacterial growth and inflammation by Nerium oleander extract with comprehensive in vivo safety profile.

BACKGROUND: Nerium oleander (L.) is well known traditionally used medicinal plant with several pharmacological activities. However, the anti-bacterial, anti-inflammatory activity and in vivo toxicity potential of floral parts of this plant are not reported. Therefore the present study was designed to investigate these activities of Nerium oleander ethanolic flower extract (NOEE) in different animal models. METHODS: Antimicrobial activity of plant extract was compared with five different antibiotics using the disk diffusion method. The time-killing kinetic assay and bacterial killing mechanism of NOEE were also performed. Anti-inflammatory activity was assessed using granuloma induced by cotton-pellet, rat paw edema induced by carrageenan and levels of different inflammatory biomarkers on healthy Wistar rats. The protein and mRNA expressions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were also measured. Acute (14 days) and sub-acute (28 days) oral toxicity studies were also performed on healthy Sprague Dawley rats. RESULTS: NOEE produced highly significant (P < 0.005) and significant (P < 0.05) zones of inhibition at 30 mg/mL and 20 mg/mL respectively against most of the tested bacterial strains. NOEE produced a more drop in viable counts of Gram-negative isolates within 20 min. After 12 h exposure with NOEE, the SEM images of MRSA showed the destruction of cell membrane. NOEE showed highly significant (P < 0.005) anti-inflammatory activity in cotton-pellet and carrageenan inflammatory models. In addition, treatment with NOEE also decreased the production of NO, PGE2, TNF-α and IL-1ß in the rat paw after treated with carrageenan. Similarly, NOEE also suppressed the inducible nitric oxide synthase (iNOS), TNF-α, IL-1ß, and cyclooxygenase-2 (COX-2) mRNA expressions. It is also showed highly significant reduction in total leukocyte count (73.09%) and C-reactive protein levels (54.60%). NOEE also inhibited COX-1, COX-2, 5-LO and 12-LO in a highly significant manner. Moreover, acute and sub-acute toxicity studies of NOEE in rats confirm the toxicity with hepatotoxicity at higher doses (2000 mg/kg) i.e. four times greater than the therapeutic dose. CONCLUSION: It is concluded that crude flower extract of N. oleander is a potent antimicrobial and anti-inflammatory agent with no toxicity potential at therapeutic doses.

Antidiarrheal potential of lactobacillus strains isolated from pharmaceutical formulations for the treatment of pediatric diarrhea.

The consumption of probiotics in the prevention and treatment of diarrhea have been clinically justified, comprehensive studied and explored in many products around the world. In Pakistan, recommendation of probiotic formulations is being emerged to control the increased mortality and morbidity from diarrhea under 5 years of age children. The objective of the study was to evaluate the antimicrobial potential of isolated Lactobacillus strains against diarrheagenic Escherichia coli. Twelve strains were isolated from different probiotic pharmaceutical formulations available in Pakistan. Physiological and biochemical characteristics of isolates were analyzed. Selective media was used for the growth of probiotic isolates and E. coli. Agar spot and well diffusion methods were employed to evaluate the antimicrobial activity of isolates and measured as a zone of inhibition (mm). Changes in cell morphology was observed by Scanning Electron Microscopy. Statistical analysis was adopted with a level of significance p<0.05. L. reuteri (28 mm) and L.plantarum (26 mm) showed significant inhibitory actions against E. coli due to increased organic acids and bacteriocins formations. Rest of isolates exhibited mild to moderate activity with an average inhibition (20 mm). L. sporogenes demonstrated weak antagonistic behavior. Use of multiple strains of Lactobacillus along with L. reuteri or L.plantarum as a therapeutic agent or in nutritional supplements could be a novel approach for the prevention and treatment of pediatric diarrhea.

Development and validation of the General Rehabilitation Adherence Scale (GRAS) in patients attending physical therapy clinics for musculoskeletal disorders.

BACKGROUND: Non-adherence to physical therapy ranges from 14 to 70%. This could adversely affect physical functioning and requires careful monitoring. Studies that describe designing and validation of adherence measuring scales are scant. There is a growing need to formulate adherence measures for this population. The aim was to develop and validate a novel tool named as the General Rehabilitation Adherence Scale (GRAS) to measure adherence to physical therapy treatment in Pakistani patients attending rehabilitation clinics for musculoskeletal disorders. METHODS: A month-long study was conducted in patients attending physical therapy sessions at clinics in two tertiary care hospitals in Karachi, Pakistan. It was done using block randomization technique. Sample size was calculated based on item-to-respondent ratio of 1:20. The GRAS was developed and validated using content validity, factor analyses, known group validity, and sensitivity analysis. Receiver operator curve analysis was used to determine cut-off value. Reliability and internal consistency were measured using test-retest method. Data was analyzed through IBM SPSS version 23. The study was ethically approved (IRB-NOV:15). RESULTS: A total of 300 responses were gathered. The response rate was 92%. The final version of GRAS contained 8 items and had a content validity index of 0.89. Sampling adequacy was satisfactory, (KMO 0.7, Bartlett's test p-value< 0.01). Exploratory factor analysis revealed a 3-factor model that was fixed and confirmed at a 2-factor model. Incremental fit indices, i.e., normed fit index, comparative fit index and Tucker Lewis index, were reported > 0.95 while absolute fit index of root mean square of error of approximation was < 0.03. These values indicated a good model fit. The value for Cronbach (α) was 0.63 while it was 0.77 for McDonald's (ω), i.e., acceptable. Test-retest reliability coefficient was 0.88, p < 0.01. Education level was observed to affect adherence (p < 0.01). A cut-off value of 12 was identified. The sensitivity and accuracy of the scale was 95%, and its specificity was 91%. CONCLUSION: The scale was validated in this study with satisfactory results. The availability of this tool would enhance monitoring for adherence as well as help clinicians and therapists address potential areas that may act as determinants of non-adherence.

Estimation of direct cost of managing rheumatoid arthritis treatment to Pakistani patients using real-world follow-up data.

OBJECTIVE: This study aimed to estimate annual direct cost attributed to rheumatoid arthritis (RA) treatment from a patient's perspective using real-world patient follow-up data from hospitals' electronic database. METHODS: A prospective 1-year study was conducted in rheumatology clinics of tertiary care hospitals of Karachi, Pakistan. Cost-of-illness methodology was used and all patient data related to costs of rheumatologist visits, physical therapy sessions, medications, assistive devices and laboratory investigations were obtained directly in printed hardcopies from patient electronic databases using their medical record numbers. Transportation cost was calculated from patient-reported log books. Data were analyzed through IBM SPSS version 23. Patients were asked to sign a written consent and the study was ethically approved. RESULTS: The mean age of patients (N = 358) was 48 years. Most patients (73.7%) were female, married (86%) and had basic education (71.8%). Average cost of rheumatologist visits was PKR 11 510.61 (USD: 72.05) while it was PKR 66 947.37 (USD: 419.07) for physical therapy sessions. On average, medicines and medical devices costs were estimated at PKR 10 104.23 (USD: 63.25) and PKR 7848.48 (USD: 49.13) respectively. Cost attributed to diagnostic and laboratory charges was PKR 1962.12 (USD: 12.28) and travel expense was PKR 6541 (USD: 40.95). The direct expenditure associated with managing RA was PKR 37 558 (USD: 235.1). All costs were reported per annum. CONCLUSION: Patient with RA in Pakistan pay a considerable amount of their income for managing their condition. Most patients have no provision for insurance which is a need considering the nature of the disease and associated productivity loss that would significantly lower income as the disease progresses.

Evaluation of prevalence of different types of cancer and its chemotherapy in various ethnic groups of Pakistan: A retrospective study

The objective of the study was to evaluate different types of cancer and its chemotherapy in various ethnic groups of Pakistan. Ethnic groups includes, Pukhtoons, Punjabis, Sindhis, Muhajirs, Siraikis, Memoons, Hazaras, Hindkos, Baltis, Gilgitis, Kashmiris, and Afghanis. The data was collected from well reputed hospitals located in the different provinces of Pakistan. The collected data was taken from 15 hospitals where around 8500 patients visited during 2010 to 2017. From the visited patients, 8356 were analyzed for their ethnicity, age and sex while, 144 patients (male 77 and female 67) were excluded from analysis due to incomplete information or loss of follow-up. Among 8356 patients, 3762 were male (45%) whereas, 4594 were female (55%). The chemotherapy was carried out as per National Comprehensive Cancer Network guidelines (NCCN- guidelines). The most common five prevalent cancer among these ethnic groups were Head and Neck, Blood, Respiratory, Genito-urinary and Breast cancer. The most common cancer in female was breast cancer while, head and neck cancer was more prevalent in male. It can be concluded that the prevalence of cancer in Pakistan is very alarming, which may be due to lack of awareness, illiteracy, lack of national cancer control programs, and economics issues.

Impact of pharmacist educational intervention on disease knowledge, rehabilitation and medication adherence, treatment-induced direct cost, health-related quality of life and satisfaction in patients with rheumatoid arthritis: study protocol for a randomized controlled trial.

BACKGROUND: The objective of this study is to evaluate the effectiveness of pharmacist intervention in improving disease knowledge, adherence to treatment, health-related quality of life (HRQoL) and direct cost of treatment. The study also documents patient satisfaction with pharmacist counselling as a quality control measure. METHODS/DESIGN: This is a randomized, single-blind, two-arm, controlled trial in patients with rheumatoid arthritis visiting outpatient rheumatology clinics in Karachi, Pakistan. We will enroll patients with established diagnosis of rheumatoid arthritis over 3 months. The patients would be randomized through a computer-generated list into the control group, i.e., usual care or into the intervention group, i.e., pharmaceutical care, in a ratio of 1:1, after providing signed written consent. The study will take place in two patient-visits over the course of 3 months. Patients in the intervention group would receive intervention from the pharmacist while those in the control group will receive usual care. Primary outcomes include change in mean score from baseline (week 0) and at follow up (week 12) in disease knowledge, adherence to medications and rehabilitation/physical therapy. The secondary outcomes include change in the mean direct cost of treatment, HRQoL and patient satisfaction with pharmacist counselling. DISCUSSION: This is a novel study that evaluates the role of the pharmacist in improving treatment outcomes in patients with rheumatoid arthritis. The results of this trial could set the foundation for future delivery of care for this patient population in Pakistan. The results of this trial would be published in a peer-reviewed journal. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03827148 . Registered on February 2019.

Assessment of killing kinetics assay and bactericidal mechanism of crude methanolic bark extract of Casuarina equisetifolia.

Casuarina equisetifolia L. is an important medicinal plant widely used to treat various diseases particularly ulcers, diabetes, cough, diarrhea and many infectious and skin diseases. The aim of this research study was to examine the killing mechanism and killing kinetics assay of methanolic bark extract of C. equisetifolia against some highly resistant human pathogens. The comparison on antibacterial activity of extract was firstly done with six different well reputed antibiotics using disk diffusion method. The broth dilution method was used to measure the MIC and MBC values. The mechanism of killing was identified by scanning electron microscopy (SEM) technique. Results showed that higher inhibitory zones were produced by methanolic plant extract than that of some tested antibiotics. The lower MIC and MBC values indicated the antibacterial potency of plant extract. The extract of C. equisetifolia produced a more drop in optical density of S. aureus, MRSA B. subtilis and S. epidermidis up to 12 hrs. The complete destruction of the cell membrane of MRSA was observed after 12 h treatment with plant extract. It is concluded that crude bark extract of C. equisetifolia is potent antimicrobial agent and produced both bacteriostatic and bactericidal effects. Its killing time was extremely faster especially against MRSA. The cell membrane rapturing is a suggested killing mechanism of plant extract.

Estimation of the Direct Cost of Poliomyelitis Rehabilitation Treatment to Pakistani Patients: A 53-Year Retrospective Study.

BACKGROUND: Pakistan is one of the last few countries in which poliomyelitis is endemic. Evidence indicates that out-of-pocket expenditures are a barrier to polio rehabilitation treatment, yet there are no reported figures related to the financial burden of this disease on patients in a recently polio-endemic country. OBJECTIVE: This study investigated direct costs attributed to rehabilitation treatment of poliomyelitis among Pakistani patients and reported its duration along with the socioeconomic status of poliomyelitis survivors. CONCLUSION: The cost of poliomyelitis rehabilitation in Pakistan is high; it has an economic effect on the lives of patients and their families. Despite good education, polio survivors in Pakistan appear to have low socioeconomic status, lower chances of employment and marriage, as well as fewer children. Further research is recommended to explore the burden of disease on society, i.e., indirect costs and suffering.

Development of Evidence-Based Disease Education Literature for Pakistani Rheumatoid Arthritis Patients.

Rheumatoid arthritis affects 0.5% to 1% of the population globally and is one of the most common causes of disability. Patient education plays a key role in improving treatment outcomes. The purpose of this study was to discuss the process involved in designing an evidence-based disease education literature for rheumatoid arthritis patients of Pakistan in Urdu language with culturally relevant illustrations. A study was conducted to develop disease education literature using Delphi consensus, content validity, and patient feedback. A panel of experts comprised of university professors and health care experts, including health practitioners and pharmacists as well as a social scientist, was set up to assess the need. Eight patients were randomly selected and were asked to give their feedback. Their feedback was incorporated in the development process. The entire process was carried out in eight steps. A disease education literature for patients of rheumatoid arthritis was developed and edited in the form of a booklet. The booklet contained evidence-based information that must be provided to patients in both Urdu and English languages with culturally relevant illustrations. The availability of such literature is significant, as it enables the patients to seek knowledge at home at their convenience. This home-based knowledge support is as helpful as any other means of medical care. The developed literature is planned to be used in further studies which will evaluate its impact in improving knowledge of RA patients.

Validation and application of high performance liquid chromatographic method for the estimation of metoclopramide hydrochloride in plasma.

The objective of this study was validation of a reverse phase HPLC method for the estimation of metoclopramide HCl in plasma already validated for determination of metoclopramide HCl in tablets dosage form. A reverse chromatographic method was used for estimation of metoclopramide HCl with the mobile phase of acetonitrile, 20mM potassium dihydrogen phosphate buffer solution (pH 3.0 adjusted with orthophosphoric acid) in the ratio of 40: 60. The column used was Waters C18 3.9×300mm µBondapak (RP). The flow rate of the mobile phase was 2ml/ minute. The detector was set at the wavelength of 275nm. This method validated in plasma and was found to be linear, with correlation coefficient (R2), value of 0.9988, in the range of 48 ng/ml-0.25ng/ml. The method modified was accurate, precise, sensitive and showed good stability results. The % RSD of the retention time and peak area of metoclopramide HCl was 0.19% and 1.44% respectively. All the parameters such as specificity, linearity, range, accuracy, precision, system suitability, solution stability, detection and quantification limits were evaluated to validate this method and were found within the acceptance limits. The method can be effectively used for estimation of metoclopramide HCl in plasma.

Comparative bioavailability and pharmacokinetic study of Cefadroxil capsules in male healthy volunteers of Pakistan.

The current study was aimed to judge bioequivalence between two formulations of cefadroxil capsules as guided by FDA guidelines. Another objective was to conduct pharmacokinetic evaluation in Pakistani population. A single-dose, randomized, cross-over pharmacokinetic study was conducted during the month of May'2013 to August'2013. Washout period was one week. Fourteen healthy male adult volunteers were enrolled in the study, however twelve completed the study. Cefadroxil plasma concentration was analyzed by using validated HPLC method. Protein precipitation was achieved by the addition of 6% tri chloro acetic acid in 1:1 ratio and detection was done at 260 nm. Retention time was 7.792 min and correlation coefficient (R2) was 0.9953 showing linearity of the method. Blood sampling was carried out at different time intervals after administration of either test (TEST 500 mg) or reference (REF® 500 mg) formulation. Pharmacokinetic parameters (AUC0→ ∞, AUC0→ t, Cmax, Tmax, t1/2 and kel) were calculated using Kinetica® PK/PD software. The geometric mean ratios and 90% confidence interval (CI) of these pharmacokinetic parameters for cefadroxil (test and reference) formulations were 0.986 (90.83-106.98%) for AUC0→ t; 0.967 (89.13-104.92%) for AUC0→ ∞ and 0.999 (91.06-109.69%) for Cmax. The differences between Tmax of both formulations were not found to be statistically significant (p-value was more than 0.05). The 90% CI of the test/reference AUC and Cmax ratio of cefadroxil were within the FDA recommended range for bioequivalence. Maximum plasma concentration Cmax was 12.5 µg/ml for test and 12.47 µg/ml for reference formulations. Average time to reach Cmax for test and reference formulation was 1.54 and 1.5 hrs. The two formulations of cefadroxil studied during the above study were verified bioequivalent. Maximum plasma concentration of cefadroxil was lower than those mentioned in some previous studies, while Tmax and half-life were near to values reported in literature.

Evaluation of Potential Drug-Drug Interactions with Antidepressants in Two Tertiary Care Hospitals.

BACKGROUND: Limited resources of healthcare system and high use of antidepressants have raised some serious concerns regarding proper surveillance system of prescribed medicines. Not much literature is available from Pakistan regarding the potential drug-drug interactions (pDDIs) associated with antidepressants. OBJECTIVE: The objective of this study was to assess the frequency of pDDIs associated with antidepressants, their severity, significance and their association with patient characteristics. MATERIALS AND METHODS: A prospective, observational study was conducted in two major hospitals of Karachi for the period of three months. Patient profiles, medication charts, and physician notes were thoroughly reviewed to gather all the relevant information. Inclusion and exclusion criteria were set prior to data collection. The collected data was then analysed using Micromedex Drug-REAX System. Descriptive and binomial logistic regression analysis was used to express results. RESULTS: Of 245 prescriptions reviewed, 141 prescriptions had at least one pDDI (57.5%). A total of 181 pDDIs were identified in prescription containing antidepressant. The ratio of pDDI per prescriptions was 0.78. 42.5% interactions were moderate in severity, 30% of interactions were rapid in onset, and 43% were considered as significant interactions. Polypharmacy (OR=3.41, p< 0.001) and presence of chronic problems (OR=2.14, p=0.002) were significantly associated with the occurrence of pDDIs. Citalopram and diclofenac (11.6%) was commonly prescribed interacting pair in this study. CONCLUSION: The findings of this study recorded high frequency of antidepressants associated pDDIs. Our results confirm the significant association of polypharmacy with the occurrence of pDDIs with antidepressants. Future studies are warranted to establish these results by including hospitals in different parts of the country.

Determination of Cefadroxil in Tablet/Capsule formulations by a validated Reverse Phase High Performance Liquid Chromatographic method.

An innovative, selective and rapid reversed phase High Performance Liquid Chromatographic (RP-HPLC) method for the analysis of cefadroxil in bulk material and oral solid dosage forms has been developed and validated. The chromatographic system consisted of Sil-20A auto sampler, LC-20A pump and SPD-20A UV/visible detector. The separation was achieved by C18 column at ambient temperature with a mobile phase consisting of methanol: Phosphate buffer (10: 90) at a flow rate of 1.5 ml/min. The method is reproducible, repeatable (%RSD for intra-day and inter-day ranged between 1.75-5.33% and 0.58-2.69%) and linear (R2=0.9935). The LOD and LOQ of the method were 0.5 and 1.0 µg/ml, respectively. The present RP-HPLC method was found to be sensitive, accurate, precise, rapid and cost effective that can be efficiently used in QC/QA laboratories for routine analysis of the raw materials as well as oral dosage formulations of cefadroxil.

Disintegrants combination: development and optimization of a cefadroxil fast disintegrating tablet.

Fast Disintegrating Tablets (FDTs) is a rapidly growing dosage form preferred for special population (pediatric, geriatric and psychotic patients). It is also developed with the aim of improving bioavailability and patient compliance. During the present study, cefadroxil fast disintegrating tablets formulations (n=9) were designed and optimized by central composite design with two independent variables (croscarmellose and crospovidone) using design expert® software. The effects of independent variables on formulation properties such as friability, hardness, in vitro dispersion and disintegration were assessed by drawing response surface graphs with design expert® software. Tablets were assessed for pharmacopeial and non-pharmacopeial parameters to ensure the quality of compressed tablets. Among all formulations, F3, F8 and F9 have shown better results. The formulation F9 containing 15mg croscarmellose and 33.075mg crospovidone showed good pharmacotechnical attributes as well as shelf life. F 9 showed improved dissolution with t90% of> 2 min and will lead to better bioavailability.

Comparative study on resistant pattern of clinical isolates against levofloxacin and cefepime.

The aim of this study is to evaluate the susceptibility and resistance pattern of clinical isolates causing different types of infections and to compare the efficacy of antibiotics namely levofloxacin and cefepime. The in-vitro antibacterial activity and resistance patterns of these two well known antibiotics were studied and compared using disk diffusion method. For this, one hundred clinical isolates comprising of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa were collected from different local pathological laboratories and hospitals. Escherichia coli (17.95% against cefepime and 30.77% against levofloxacin), Staphylococcus aureus (30% against cefepime and 46.66% against levofloxacin) and Pseudomonas aeruginosa (23.53% against cefepime and 35.29% against levofloxacin) were found resistant against the studied antibiotics which show that cefepime is more effective than levofloxacin. In case of Klebsiella pneumoniae, resistance was 42.85% against cefepime and 35.71% against levofloxacin thereby showing that levofloxacin is more effective than cefepime. Concluded that the clinical isolates collected were susceptible to both the antibiotics but the microbial resistance against these antibiotics is increasing in our population which is alarming. Therefore, it is recommended the physicians may prescribe these antibiotics unless no other substitute is available in clinical practice.

Efficacy of newly formulated ointment containing 20% active antimicrobial honey in treatment of burn wound infections.

BACKGROUND: Honey has been familiar to possess antimicrobial potential to clear infection against burn wound infecting bacteria since ancient times. The objective of the study was to evaluate the efficacy of the newly formulated honey ointment during the treatment of burn wound infections. The Experimental (Non comparative) study was conducted at outpatient department of Dermatology, Fauji Foundation Hospital, Rawalpindi from November 2009 to October 2010. METHODS: The antimicrobial activity of different Pakistani floral sources (Acacia nilotica species indica, Zizyphus, Helianthus annuus and Carisa opaca) honey samples were investigated by disc diffusion method against freshly isolated burn wounds infecting bacteria. Ointment containing 20% active antimicrobial honey was formulated as a sovereign remedy. A total number of twenty patients with second degree of burn wounds on different parts of the body were studied. A thin layer of honey ointment on gauze was applied to the wounds two to three times a day up to the complete healing. RESULTS: During microbiological study, Pakistani honey samples were discovered to exhibit a very promising antimicrobial activity against all the wound infecting microorganisms tested. Clinical trials demonstrated that the topical application of honey ointment have significant control of infections arising form pathogenic bacteria and up to 100% healing results were observed in all burn wound cases within mean healing time for the duration of 8.15 (3-18) days time period. CONCLUSION: Newly formulated ointment containing 20% active antimicrobial honey is more effective and low-cost alternative preparation for the treatment of burn wound infections.

'Honey ointment': a natural remedy of skin wound infections.

BACKGROUND: Honey is a gift of nature, principally identified and valued to possess antimicrobial and anti-inflammatory activity and has been used as a natural remedy of wounds since ancient times. The objectives of this study were to evaluate the antimicrobial activity of honey against micro-organisms, to formulate a honey ointment and to evaluate the efficacy of such ointment by conducting clinical trials on skin wound infection. METHODS: This experimental study was conducted at Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi and Out-patient Department of Dermatology, Fauji Foundation Hospital, Rawalpindi from November 2009 to October 2010. The antimicrobial activity of Pakistani floral sources (Trachysperm copticum, Acacia nilotica species indica, Zizyphus) honey samples was investigated by disc diffusion method against freshly isolated wound infecting bacteria (Staphylococci aureus, Staphylococci epidermidis, Streptococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli, Proteus vulgaris and Candida albicans), and Staphylococci aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9022, Escherichia coli ATCC 25922, Candida albican ATCC 15146. An ointment containing 20% active antimicrobial honey was formulated. The efficacy of such ointment was evaluated by passing thought clinical trials. A total number of 27 patients (23 skin wound infection, and 4 diabetic foot ulcer) were involved in the study. Thin layer of newly formulated honey ointment on gauze were applied two to three times per day till complete healing. RESULTS: In microbiological assay the honey samples were found to exhibit a very promising antimicrobial activity against all the micro-organisms tested. In clinical trial very significant results (99.15%) healing was observed in skin wound infections cases with mean healing time of 5.86 (2-20) days, and 95% diabetic foot ulcers healed with the mean healing time of 20 (8-40) days. CONCLUSION: Newly formulated ointment containing 20% active antimicrobial honey is very effective and alternative low-cost product for the treatment of wound infections.