Impact of different organic acids on solubility enhancement of cefpodxime proxetil immediate release tablet and its stability studies

Cefpodoxime proxetil is a third generation cephalosporin antibiotic demonstrates pH dependent solubility and is highly soluble only in acidic pH. The purpose of this investigation was to design and develop immediate release tablets of cefpodoxime proxetil by direct compression method and determine the effect of different solid buffers [organic acids] such as fumaric acid [formulations F1-F4], maleic acid [formulations M1-M4] and citric acid [formulations C1- C4] by using cefpodoxime and acid in the ratios of 4:1, 2:1, 1:1 and 1:2 to achieve pH-independent release of the drug. Physical parameters and assay were found to be within the acceptable range as prescribed in USP 36 / NF 31. In vitro dissolution studies of each formulation were performed in distilled water, USP dissolution medium, HCl buffer solution of pH 1.2, phosphate buffer solutions of pH 4.5 and 6.8 to observe the drug release. The formulations F3, F4, M4 were selected for film coating on the basis of better drug release profile, to protect the drug from chemical degradation through hydrolysis. Film coated formulation F3, F4 and M4 showed a remarkable in vitro release of the drug [72.88+/-0.43 to 92.67+/-0.71%] within 30min of observation in all dissolution media and further evaluated by model independent and model dependent approaches. The drug release was found to be best fit to Weibull model as highest r[2] [adjusted] [0.924- 0.998] and lowest AIC [18.416-54.710] values were obtained in all dissolution media. R Gui[registered sign] applied for stability studies of F3 and F4 formulations, showing shelf lives of 28 and 27months at ambient and 33 months at accelerated temperatures. Formulation F4 was chosen as best formulation on the basis of physical properties, highest dissolution rate and stability studies

Formulation development and comparative in vitro study of metoprolol tartrate [IR] tablets

The objective of the present work was to develop Immediate Release [IR] tablets of Metoprolol Tartrate [MT] and to compare trial formulations to a reference product. Six formulations [F1-F6] were designed using central composite method and compared to a reference brand [A]. Two marketed products [brands B and C] were also evaluated. F1-F6 were prepared with Avicel PH101 [filler], Crospovidone [disintegrant] and Magnesium Stearate [lubricant] by direct compression. Pharmacopoeial and non-pharmacopoeial methods were used to assess their quality. Furthermore, drug profiles were characterized using model dependent and independent [f2] approaches. Brands B and C and F5 and F6 did not qualify the tests for content uniformity. Moreover, brand B did not meet weight variation criteria and brand C did not satisfy requirements for single point dissolution test. Of the trial formulations, F2 failed the test for uniformity in thickness while F4 did not disintegrate within time limit. Only F1 and F3 met all quality parameters and were subjected to accelerated stability testing without significant alterations in their physicochemical characteristics. Based on AIC and r2adjusted values obtained by applying various kinetic models, drug release was determined to most closely follow Hixson-Crowell cube root law. F1 was determined to be the optimized formulation

Formulation development and optimization: Encapsulated system of atenolol and Glyburide

Purpose: Objective of this study is to develop; tablet- in- a capsule system, to deliver Atenolol 25mg and Glyburide 5mg in the hard gelatin capsule. In order to improve patient compliance and reduce problems associated with complex therapeutic regimen Atenolol [cardio-selective beta-blocker] and Glyburide [anti-diabetic; sulfonylurea] are commonly, prescribed to the diabetic hypertensive patient

Method: In present work six different formulations of Atenolol [AF1-AF6] and Glyburide [GF1-GF6] were prepared by direct compression method using Avicel, Lactose DC, Crospovidone and Magnesium Stearate in different proportions and encapsulated in hard gelatin shells. Post compression parameters i.e. weight variation, diameter variation, thickness variation, hardness variation,% friability, disintegration,% drug release were determined at different pH 1.2, 4.5 and 6.8, and subjected to dissolution profile comparison through similarity factor [f[2]]

Results: Stability studies were performed and shelf lives were calculated by R-Gui Stab R console 2.15.2 and determined to be 15and 27 months for Atenolol and Glyburide respectively. The percentage drug contents of Atenolol and Glyburide were estimated spectrophotometerically at 286nm and 314.7nm respectively. Formulations CF1-CF6 [encapsulated] were subjected to weight variation, disintegration and dissolution tests and subjected to model dependant analysis for dissolution studies. The simultaneous quantitation of Atenolol and Glyburide for content assay was done by HPLC method of analysis

Conclusion: formulation CF6 is showing highest coefficient of correlation values for all models applied. So we can conclude that the proposed system can improve patient compliance by increasing the ease of administration of two drugs together

Simultaneous quantitation of Ofloxacin, Fexofenadine HCl and Diclofenac Potassium in affixed dose combinative formulation by HPLC-UV method

A high-pressure liquid chromatography [HPLC-UV] based simple and specific method for simultaneous quantitative determination of Ofloxacin, Fexofenadine HCl and Diclofenac Potassium has been developed and validated according to ICH guidelines. Chromatographic separation of the three drugs was carried out on 4.6 x 250mm x 5micro Licrospher RP Select B Column, using mobile phase constituted of methanol and phosphate buffer pH 3.5 [650: 350], pH adjusted to 3.5 +/- 0.05 with dilute ortho-phosphoric acid and delivered at a flow rate of 1ml/min. The eluents were detected at UV wavelength of 220nm and the retention times for Ofloxacin, Fexofenadine HCl and Diclofenac Potassium were 2.5 minutes, 4 minutes and 11.5 minutes, respectively. This method is suitable and specific for the three drugs and was found to be linear [R2>0.996], accurate, specific, reproducible and robust over a concentration range of 0.05 to 0.15mg/ml for Ofloxacin, 0.015 to 0.045mg/ml for Fexofenadine HCl and 0.0125 to 0.0375mg/ml for Diclofenac Potassium. The proposed method is simple and convenient, hence easily utilized for the characterization and quantitation of the three drugs in a single formulation for combination therapy of rheumatoid arthritis, sepsis, infection with fever and flu

Quality evaluation and in vitro interaction studies between levofloxacin 250mg and diclofenac sodium 50mg tablets

Fluoroquinolones are broad-spectrum antibiotics, work against Gram-positive and Gram-negative bacteria and are a clinically proven option for many resistant infections. Among fluoroquinolones Levofloxacin works best against acute sinusitis, inflammation of the lower airways, acute exacerbation of chronic bronchitis, community acquired pneumonia, complicated urinary tract infection including Pyelonephritis, chronic bacterial prostatitis and skin and soft tissue infection. Levofloxacin is a frequently prescribed antibacterial agent with Diclofenac Sodium for pain management in infectious conditions. The objective of the present work is to evaluate the level of interaction between Levofloxacin and Diclofenac Sodium. In this work market available brands of both drugs were also evaluated for quality. The physiochemical parameters like weight variation, thickness variation, and mechanical strength were determined. Similarly the percentage drug release and content uniformity test were also analyzed; the tested quality attributes were found within the recommended pharmacopeia ranges except brand L6 that had high drug content 124.629 +/- 3.614 while brand L[4] and L[5] were not found similar in pH 1.2. When subjected to model dependent analysis Levofloxacin showed compliance with [first order, Higuchi, Hixson Crowell and Weibull] at pH [1.2, 4.5 and 6.8]. However Diclofenac Sodium showed adherence with [first order, Hixson Crowell and Weibull] at pH [1.2, 4.5 and 6.8] but following Higuchi at pH 1.2 and 4.5 only. The interaction studies were also performed spectrophotometrically and simultaneous equation was used to estimate the percentage availability of both the drugs at pH 4.5, 6.8, FaSSGF and FaSSIF. The studies showed that the percent availability of Levofloxacin was increased significantly in FaSSIF i.e. 129.173 +/- 0.323 at 45 minutes in the presence of Diclofenac Sodium

Formulation development of intermediate release Nimesulide tablets by CCRD for IVIVC studies

Simple and cost effective study consisting of three steps, comparison of micromeritic properties of different blends i.e. placebo without API and Nimesulide containing, Use of central composite design [CCRD] for intermediate release Nimesulide tablets and stability results of three selected Nimesulide tablet formulations which were calculated by using R Gui. Different concentrations of Avicel, hydroxypropyl methyl cellulose [HPMC] and magnesium stearate were used as variables in central composite design and two types blend i.e., with or without Nimesulide were selected for bulk density, tap density, percentage compressibility; angle of repose and Hausner's ratio. Blending rate constant was performed after applying the different mixing times like 3, 6, 9 and 12 minutes. Twenty intermediate release formulations were designed and three formulations were chosen for compression by direct compression method on the basis of compressibility index. Physicochemical properties and best release pattern in four hours in different dissolution medium were successfully measured. Relative densities, porosity of tablets were compared with tensile strength of tablet and weight variation, hardness, friability and dissolution was performed by simple experiments. Presence of Nimesulide in the bulk increased all micromeratic tests while 9 minutes was best mixing time. The hardness of NM containing tablets increased with the increase of relative density. The release pattern was further analyzed by model dependent i.e. zero order, first order and Higuchi, Korse-meyer and Pappas, Hixson Crowell and model independent kinetic model i.e., f2 value respectively. R Gui explained the F16 formulation shows the best result in stability studies with shelf life 72 months

Practice nurses and pharmacists: a perspective on the expectation and experience of nurses for future collaboration

To explore the nurses' expectations and experience about pharmacists in private sector hospitals of Karachi, Pakistan. A cross-sectional study was conducted from June to September 2012 in five private sector hospitals of Karachi, Pakistan. A convenient sample of nurses [n=377] were enrolled in this study. Data was obtained through a previously validated questionnaire. Responses were statistically analyzed using SPSSv.17. Questionnaires were returned giving a response rate of 63.6% of which 20 were unusable [n=240]. Out of the remaining 220, 24.1% [n=53] responded that they never or rarely interacted with a pharmacist. Respondents who expect pharmacists to collaborate with nurses to solve drug related problems were 45% [n=99]. Nurses' experience of pharmacists was not substantial as only 44.5% [n=98] respondents consider pharmacists as a reliable source of clinical drug information. The role of pharmacists is not well appreciated among nurses in Pakistan. Hence, pharmacists must bridge the observed gap and use a more strategic and consistent approach to build a more positive image in line with other healthcare professionals and in providing patient-centred pharmaceutical care. This research would impress upon the pharmacists the need to redefine their role in the healthcare settings

Incidence of medication error associated with the use of beta-blockers in Pakistan

Medication errors [ME] are human errors, which are very frequent in cardiovascular patients and result in patient morbidity and mortality. This study was focused to evaluate the quality of prescriptions and to emphasize the placement of clinical pharmacist in health care team. This study was carried out in different outpatient settings of [in] Karachi, Pakistan. The study period was June'2011 till June'2012. Retrospective data was analyzed for the outpatients' prescription of beta blocker drugs. During the study, prescriptions [n=450] were collected from different outpatient settings of [in] Karachi, Pakistan. Prescription containing beta-blockers were analyzed for the essential elements to be mentioned in prescription. Drug-drug interactions were identified by the Micromedex.2.0 Drug-Reax database and severity of medication error was determined by NCCMERP Index. A total of 1627 medication errors were identified in 450 prescriptions. The most frequent error was not mentioning the patient's weight [95%], followed by missing diagnosis [79.4%] and drug-drug interactions [69.5%]. Twenty-two prescriptions were placed in the most severe category I [4.88%]. Average number of drugs per prescription was 4.76. Significant difference was observed [x[2]=52.418, p<0.05] using SPSS 19 for those prescription orders having more than 5 drugs with Beta-blockers. This indicates that the errors in prescription such as drug-drug interactions, wrong dose etc. was significantly increased with the number of drugs per prescription. Results showed that medication errors are very frequent in prescription written in outpatient setting of various hospitals and clinics in Karachi. This shows that the irrational prescribing is a common practice in developing countries. Placement of skilled pharmacist in the health care system is the only solution for avoidance of these medication related problems.

Staphylococcal resistance against five groups of life saving antibiotics in the year 2003-2005

In the year 2003 to 2005 a prospective study was conducted to find out the predominance of Staphylococcus [Staphylococcus aureus] resistance pattern in opposition to five life saving antibiotics as these are the sole agents to treat critically ill patients in hospitals. During the period of two years almost 2500 samples of bacterial culture were taken from different pathological laboratories and hospitals in Karachi. Among these 1500 were Gram positive cocci and 1000 samples were identified as Staphylococcus aureus. Life saving antibiotics were taken from five different groups and by mean of disk diffusion technique antibiogram of Staphylococcus aureus against these antibiotic were determined. During the course of study imipenem showed 11%, amikacin exhibited 58%, cefipime showed 31%, vancomycin and piperacillin/tazobactam displayed 24% resistance against Staphylococcus aureus. Imipenem was found to be most effective against Staphylococcus aureus.Resistance to other antibiotics developed quickly in Staphylococcus aureus collected from clinical areas where these antimicrobial agents are extensively used

Formulation development and evaluation of diltiazem HCl sustained release matrix tablets using HPMC K4M and K100M

The aim of this study was to develop a sustained release hydrophilic matrix tablet of Diltiazem HCl and evaluates the effect of formulation variables [e.g. lubricant, binder, polymer content and viscosity grades of HPMC] on drug release. Twelve different formulations [F1-F12] were prepared by direct compression. The results of the physical parameters and assay were found to be within the acceptable range. Rate of drug release was found to be slow as the fraction of the polymer was increased from 20-50%. The drug release rate from tablets containing K4M was effectively controlled by increasing the talc concentration, whereas the burst effect was reduced by increasing binder content. The drug release was higher with K4M as compare to K100M. Model-dependent and independent methods were used for data analysis and the best results were observed for K4M in Higuchi [R[2]=0.9903-0.9962] and K100M in Baker and Lonsdale [R[2]=0.9779-0.9941]. The release mechanism of all formulations was non-Fickian. F7 [50% K4M, 2% talc, 10% Avicel PH101] and F11 [40% K100M] were very close to targeted release profile. F12 [50% K100M] exhibited highest degree of swelling and lowest erosion. The f[1] and f[2] test were performed taking F11 as a reference formulation

Preparation, characterization and release of verapamil hydrochloride from polycaprolactone/ acrylic acid [PCL/AA] hydrogels

In this study pH sensitive, biocompatible and controlled released hydrgels were prepared and their localized drug delivery effect was analyzed. Polycaprolactone and acrylic acid [PCL/AA] were reacted by free radical polymerization and developed inter penetrating polymeric network [IPN] hydrogels. Benzylperoxide was used as initiator and N, N methylenebisacrylamide [NNMBisAm] was employed as a cross-linking agent. Different concentrations of monomer, polymer and cross-linking agent were used and the reaction parameters were optimized. The obtained PCL/AA hydrogels were fully characterized by Fourier transform infrared spectroscopy [FT-IR], scanning electron microscopy [SEM], and thermogravimetric analysis [TGA] that determined the polymer structure, its morphology and strength respectively. Verapamil, a calcium channel blocker was loaded by incubation of polymerization method. Controlled release Verapamil hydrogel was developed due to its low solubility; low permeability and having very short half life of 1.2-2 h. The dynamic swelling, equilibrium swelling and drug release were carried out in a buffer solution of pH 1.2, 4.5 and 6.8. Concentration of Acrylic acid showed direct, while Polycaprolactone inverse relation to swelling and drug release due to their hydrophilic and hydrophobic nature respectively. Cross-linking agent also had the contrary effect on swelling. Diffusion coefficient [D] of hydrogels was determined by using Flory-Rehner theory. Drug release and swelling data were analyzed by different kinetic models, like Zero order, First order, Higuchi, Korsmeyer's and Peppas. The release and diffusion was best described by the first order kinetics where n value was <0.5 for all the formulations indicating Fickian drug release mechanism

Development of Rp-HPLC method for fexofenadine determination in tablet formulations and development of dissolution method

Fexofenadine hydrochloride is a piperidine derivative. It is indicated to relive signs and symptoms that are related with seasonal allergic rhinitis, such as rhinorrhea, sneezing, nose, throat and itchy eyes. In the present research work a liquid chromatographic method was developed for the determination of Fexofenadine in tablets and the dissolution method by UV/VIS spectrophotometer was also developed. Method was developed by using Lichrospher 10 micro m [C18] column. The mobile phase is composed of acetonitrile-5mM ammonium acetate buffer [50:50, v/v] pumped at a flow rate of 1 ml/min. The UV detector was operated at 254nm. The method was validated for system suitability, accuracy/recovery, linearity, system precision, method precision, ruggedness, robustness, limit of detection and limit of quantitation. Similarly, for dissolution method difference concentrations of standard and sample solutions were prepared i.e. 65 micro g/ml, 35 micro g/ml, 17.5 micro g/ml, 8.75 micro g/ml and 4.375 micro g/ml. The proposed HPLC method was easy, precise and fewer time consuming. The linearity for the dissolution method was found to be acceptable. The correlation coefficient of standard solutions was 0.9979 similarly the correlation coefficient of sample solutions was 0.9963

Pharmacokinetic study of cephradine in Pakistani healthy male volunteers

To observe and discuss the difference in the pharmacokinetics of Cephradine in Pakistani population with the reported data of other ethnic origins. A Single group pharmacokinetic study was conducted having six healthy male volunteers of 20-24 years of age. Blood samples were collected at appropriate times up to 7 hours. Plasma concentrations of Cephradine was determined by HPLC technique and pharmacokinetic parameters were determined by both compartmental and noncompartmental methods using Kinetica ver 4.4.1 and Winnonlin ver 5.01. Peak plasma concentration was 11.49 +/- 1.73 microg/ml achieved at 0.76 +/- 0.12 hr, after the administration of 250 mg Cephradine to fasting volunteers. Area under the serum concentration-time curve was found to be 16.4 +/- 1.71 microg.hr/ml. Absorption, distribution, disposition and elimination half lives were calculated as 0.183 +/- 0.038hr, 0.248 +/- 0.143 hr, 2.126 +/- 0.341 hr and 0.441 +/- 0.193 hr respectively where as the volume of central compartment and total body clearance were found to be 9.65 +/- 3.78 L and 15.4 +/- 1.89 L/hr. The plasma concentration time curves showed the absorption rate constant was 3.968 +/- 0.05 hr-1, disposition rate constant was 0.333 +/- 0.05 hr-1, distribution rate constant was 3.64 +/- 2.18 hr-1 and elimination rate constant was 1.738 +/- 0.468 hr-1. The value of micro-constants i.e. K12 [central to peripheral compartment] and K21 [peripheral to central compartment] were found to be 1.529 +/- 1.499 hr-1 and 0.704 +/- 0.44 hr-1 respectively, where as MRT and AUMC were calculated as 2.04 +/- 0.09 hr and 35.92 +/- 1.86 hr[2]x micro g/mL. The findings showed that the results of Pakistani subjects are slightly different when compared with the reported data of other ethnic origin

Evaluation of drug release kinetics from ibuprofen matrix tablets using HPMC

The aim of this study is to develop a once-daily sustained release matrix tablet of ibuprofen using hydroxypropyl methylcellulose [HPMC] as release controlling factor and to evaluate drug release parameters as per various release kinetic models. In order to achieve required sustained release profile tablets were directly compressed using Avicel pH 101 and Magnesium stearate. The formulated tablets were also characterized by physical and chemical parameters and results were found in acceptable limits. Different dissolution models were applied to drug release data in order to evaluate release mechanisms and kinetics. Criteria for selecting the most appropriate model was based on linearity [coefficient of correlation]. The drug release data fit well to the Higuchi expression. Drug release mechanism was found as a complex mixture of diffusion, swelling and erosion

Use of avicel and spray dried lactose in the development of levofloxacin 250mg tablets by direct compression method

In present study a formulation of Levofloxacin tablet 250mg was prepared by direct compression method, using two directly compressible excepients, i.e Avicel PH101 [62.5mg] and spray dried lactose [62.5mg] with magnesium stearate [5mg] as lubricant glidant on Erweka single punch machine. These tablets are round in shape having mean weight of 373.55 +/- 8.463mg with mean diameter and thickness of 12.3 +/- 0.03mm and 2.4 +/- 0.11mm. The hardness of the tablets was 12 +/- 0.39kg. Friability of tablets were 0.67% using Roche friabilator and disintegration time was 10 min in Erweka basket rack assembly. Dissolution test was performed on USP apparatus-I and%Q was found to be 94.59. Assay results was 100.54% when performed by HPLC technique using CIS column. This formulation gives excellent results using minimal excepient and simple manufacturing procedure. This type of work gives direction to try to make formulation simple and cost effective. As direct compression method is not cheap in terms of raw materials but also produces batch in short period of time. Moreover considering biopharmaceutical aspects, tablet manufactured by direct compression dissolved rapidly in gastrointestinal tract due to prime particle dissociation as compared to that of wet granulation method