QUALITY AND AFFORDABILITY OF AMOXICILLIN GENERIC PRODUCTS: A PATIENT CONCERN

Objective: Antibiotics save millions of lives from infectious diseases worldwide. Failing treatment, serious adverse effects, and antimicrobial resistance are constantly reported mainly from developing nations due to lack of quality of antibiotics medicines. In India quality of medicines remains a major regulatory challenge and patients concern. Thus, a pilot study to explore the quality of generic amoxicillin products and associated price along with their burden on patients was evaluated.Methods: 46 amoxicillin trihydrate generic products with the label claim of 250 mg amoxicillin were procured from open market of Northern India without prescription. Identification and quantitative evaluations of these generic products were estimated using Indian Pharmacopoeia (IP) 2010 recommended High-Performance Liquid Chromatography (HPLC) method. And assay value was compared with the maximum retail price per unit dosage. Affordability was estimated in general for the population who daily live on less than Indian rupees Rs. 144 and `88.6.Results: Out of 46 products, 28.26% were found to be out of IP specification, including 13.04% products which were of substandard quality. Fishers' exact test with p-value 0.87 showed products quality gaps were irrespective of their price. Ceiling price of Rs. 3.04 per unit dosage pose a high burden on the patients who are on amoxicillin treatment.Conclusion: Situation demands the evidence of safety before approval and thereafter too. However, the situation may become worst if the price and quality could not be controlled. Thus Indian drug regulatory bodies need to be entreated to counter these critical issues.Â

P-glycoprotein-dependent pharmacokinetics of irinotecan and its active metabolite, SN-38 in rats: Effect of verapamil

We have recently demonstrated that the oral bioavailability of irinotecan (80 mg/kg) can be increased at least 7-fold by co-administration of the P-gp blocker verapamil (25 mg/kg, Oral). As a result, co-treatment with P-gp inhibitor could be a useful strategy for bioavailability enhancement. However, in view of narrow therapeutic index, the co-administration of irinotecan and verapamil may result in unanticipated toxicities. Therefore, dose optimisation studies of irinotecan were performed when it is given in conjunction with a P-gp inhibitor. For dose optimization study, the bioavailability and pharmacokinetic parameters were studied in rats after oral administration of irinotecan at three doses (i.e. 20, 40 and 80 mg/kg) alone and in combination with verapamil (25 mg/kg, oral). The area under the plasma-concentration time curve (AUC) of irinotecan at 20, 40 and 80 mg/kg was 3.51 ± 1.20, 8.81 ± 1.93 and 14.03 ± 2.18 h µg/ml, respectively which after treatment with verapamil, increased dose dependently to 7.84 ± 1.20, 19.94 ± 2.39 and 61.71 ± 15.0 h µg/ml, respectively. In addition to irinotecan, plasma concentrations of SN-38, one of the major active metabolite of irinotecan, were also monitored. The less than proportional increase in SN-38 AUC from 20 to 80 mg/kg is consistent with the saturation of carboxylesterase. Our results indicate that oral drug treatment of irinotecan in presence of temporary P-gp inhibition could be as equally safe and effective as intravenous administration. Nevertheless, safe P-gp inhibitors need to be identified as alternatives to verapamil for development of efficacious oral irinotecan formulations

Lungs deposition and pharmacokinetic study of submicron budesonide particles in Wistar rats intended for immediate effect in asthma

The purpose of the present investigation was to study the aerosolization, lungs deposition and pharmacokinetic study of inhalable submicron particles of budesonide in male Wistar rats. Submicron particles were prepared by antisolvent nanoprecipitation method and freeze-dried to obtain free flowing powder. The freeze-drying process yielded dry powder with desirable aerodynamic properties for inhalation therapy. An in-house model inhaler was designed to deliver medicine to lungs, optimized at dose level of 10 mg for 30 sec of fluidization. The in vitro aerosolization study demonstrates that submicron particles dissolve faster with improved aerosolization effect as compared to micronized budesonide. Both submicron and micron particles were compared for in vivo lungs dep- osition. The results showed that relatively high quantity of submicron particles reaches deep into the lungs as compared to micron particles. Most pronounced effect observed with submicron particles from pharmacokinetic parameters was the enhancement in peak plasma concentration (Cmax) by 28.85 %, and increase in area under concentration curve (AUC0–8h) by 30.33 % compared to micron sized particles. The results suggested that devel- oped submicronized formulation of budesonide can be used for pulmonary drug delivery for high deposition to deep lungs tissues

Razvoj i in vitro vrednovanje puferiranog bioadhezivnog vaginalnog gela za miješane vaginalne infekcije

An acid buffering bioadhesive vaginal (ABBV) gel was developed for the treatment of mixed vaginal infections. Different bioadhesive polymers were evaluated on the basis of their bioadhesive strength, stability and drug release properties. Bioadhesion and release studies showed that guar gum, xanthan gum and hydroxypropylmethylcellulose K4M formed a good combination of bioadhesive polymers to develop the ABBV gel. Mono sodium citrate was used as an acid buffering agent to provide acidic pH (4.4). The drugs clotrimazole (antifungal) and metronidazole (antiprotozoal as well as antibacterial) were used in the formulation along with Lactobacillus spores to treat mixed vaginal infections. The ex vivo retention study showed that the bioadhesive polymers hold the gel for 12-13 hours inside the vaginal tube. Results of the in vitro antimicrobial study indicated that the ABBV gel had better antimicrobial action than the commercial intravaginal drug delivery systems and retention was prolonged in an ex vivo retention experiment.U radu je opisan razvoj puferiranog biodhezivnog vaginalnog (acid buffering bioadhesive vaginal, ABBV) gela za terapiju miješanih vaginalnih infekcija. Ispitani su različiti bioadhezivni polimeri procijenjena su njihova bioadhezivna svojstva, stabilnost i sposobnost oslobađanja ljekovite tvari. Guar guma, ksantan guma i hidroksipropilmetilceluloza K4M tvore dobru kombinaciju za ABBV gel. Mono natrijev citrat upotrebljen je kao puferirajuća tvar koja omogućava blago kiseli pH (4,4), a kao ljekovite tvari upotrebljeni su klotrimazol (antimikotik) i metronidazol (antiprotozoik i antibakterijsko sredstvo), zajedno sa sporama Lactobacillus. Pripravci su upotrebljeni u terapiji miješanih vaginalnih infekcija. Pokusi ex vivo pokazali su da se bioadhezivni gel zadržava u vagini 12-13 sati. Rezultati in vitro ispitivanja ukazuju na to da ABBV gel ima bolje antibakterijsko djelovanje i dulje zadržavanje od intravaginalnog sustava koji je dostupan na tržištu

Miscellaneous topics

This section includes topics that are covered in varying degrees in pharmacy programmes around the world. Microbiology, extemporaneous compounding, regulatory affairs and packaging are integral components of drug development and the manufacturing process. A number of pharmaceutical preparations such as parenteral products, ophthalmic formulations, dialysis solutions and implants are required to be sterile

Miscellaneous topics

This section includes topics that are covered in varying degrees in pharmacy programmes around the world. Microbiology, extemporaneous compounding, regulatory affairs and packaging are integral components of drug development and the manufacturing process. A number of pharmaceutical preparations such as parenteral products, ophthalmic formulations, dialysis solutions and implants are required to be sterile

Diffuse reflectance near infrared-chemometric methods development and validation of amoxicillin capsule formulations

Objective: The aim of present study was to establish near infrared-chemometric methods that could be effectively used for quality profiling through identification and quantification of amoxicillin (AMOX) in formulated capsule which were similar to commercial products. In order to evaluate a large number of market products easily and quickly, these methods were modeled. Materials and Methods: Thermo Scientific Antaris II near infrared analyzer with TQ Analyst Chemometric Software were used for the development and validation of the identification and quantification models. Several AMOX formulations were composed with four excipients microcrystalline cellulose, magnesium stearate, croscarmellose sodium and colloidal silicon dioxide. Development includes quadratic mixture formulation design, near infrared spectrum acquisition, spectral pretreatment and outlier detection. According to prescribed guidelines by International Conference on Harmonization (ICH) and European Medicine Agency (EMA) developed methods were validated in terms of specificity, accuracy, precision, linearity, and robustness. Results: On diffuse reflectance mode, an identification model based on discriminant analysis was successfully processed with 76 formulations; and same samples were also used for quantitative analysis using partial least square algorithm with four latent variables and 0.9937 correlation of coefficient followed by 2.17% root mean square error of calibration (RMSEC), 2.38% root mean square error of prediction (RMSEP), 2.43% root mean square error of cross-validation (RMSECV). Conclusion: Proposed model established a good relationship between the spectral information and AMOX identity as well as content. Resulted values show the performance of the proposed models which offers alternate choice for AMOX capsule evaluation, relative to that of well-established high-performance liquid chromatography method. Ultimately three commercial products were successfully evaluated using developed methods

Advanced drug-delivery systems

[Extract] Over the past decade, despite the importance of the biotechnology industry and increasing expenditure in research and development, there have been only a limited number of drugs originating from large pharmaceutical companies. The pharmaceutical industry has turned its attention to advanced drug-delivery systems such as pulmonary, transdermal, rectal and vaginal, proteins and gene, nasal, buccal and opthalmic, parenteral, total parenteral nutrition (TPN) and aerosol delivery, and these are the focus of this test. The philosophy behind these delivery systems is to increase therapeutic effects while decreasing toxicity by increasing the drug in the vicinity of the target cells and reducing drug exposure to non-target cells. The benefits of this approach include patient adherence and acceptance of their medications, improved outcomes and a reduction in adverse effects. The medications are such that they may be given to outpatients, resulting in a reduction in the overall use of medical resources