Lag Time Release Research Articles

Formulation and Evaluation of Colon Targeted Ciprofloxacin Microspheres

In the present study, Colon-targeted Ciprofloxacin hydrochloride microspheres were formulated and their in vitro properties were assessed to determine whether or not the antibiotic could be delivered to the colon. By utilizing span-80 as an emulsifying agent, ciprofloxacin hydrochloride microspheres for colon targeting were prepared using the emulsion-solvent evaporation method. According to the preliminary trial findings, the ratio of drug to polymer had an impact on the microspheres' properties. The Ciprofloxacin: Eudragit S-100+HPMC 6cps ratio of 1:1, 1:2, 1:3, 1:4, 1:5, and 1:6 were used to make the colon targeting microspheres, in which the ratio of Eudragit S-100 to HPMC was always 1:1. The combination of Eudragit S-100 and HPMC demonstrated increased release lag time and regulated release rate, which improved protection of the drug-containing core. For the majority of the formulations examined, zero-order release followed a time delay caused by the hydrogel's swelling/retarding behaviour before the medication started to come out of the microspheres. The colon-targeting microspheres were also tested for micrometrics, particle size and surface properties, percentage drug content, encapsulation effectiveness, and in vitro drug release study in the three different pH environments (0.1 N HCL, Phosphate buffer pH 6.8 and Phosphate buffer pH 7.4) for 12 hours. The kinetics of drug release in vitro and the drug release mechanism of the microspheres were further investigated. With a particle size of 58.9 m, an almost spherical shape, and free-flowing characteristics, the best formulation batch had the highest drug entrapment efficiency of 86.81%. It was followed by a zero-order rate release with a non-fiction-diffusion mechanism, which had an 82.77% drug release rate.

Overview on pulsatile drug delivery system

Traditionally, drugs are released in an immediate or extended fashion. However, in recent years, pulsatile drug release systems are gaining growing interest. Pulsatile drug delivery systems are developed to deliver drug according to circadian behavior of diseases. The product follow a sigmoidal drug release profile characterized by a time period of no release (lag time) followed by a rapid and complete drug release. Pulsatile systems are gaining a lot of interest as they deliver the drug at the right site of action at the right time and in the right amount, thus providing spatial and temporal delivery and increasing patient compliance. Pulsatile release systems can be classified in multiple-pulse and single-pulse systems. A popular class of single-pulse systems is that of rupturable dosage forms. Other systems consist of a drug-containing core, covered by a swelling layer and an outer insoluble, but semipermeable polymer coating or membrane. The potential benefits of chronotherapeutics have been investigated and established for number of diseases like asthma, arthritis, cancer, diabetes, epilepsy, hypertension, ulcer, hypercholesterolemia etc.

FORMULATION AND CHARACTERIZATION OF CLARITHROMYCIN FLOATING TABLETS BY USING VARIOUS POLYMERS

The present study outlines a systematic approach for designing and development of Clarithromycin floating tablets to enhance the bioavailability and therapeutic efficacy of the drug. Floating tablets of Clarithromycin have shown sustained release there by proper duration of action at a particular site and are designed to prolong the gastric residence time after oral administration. Different formulations were formulated by using direct compression technique. A floating drug delivery system (FDDS) was developed by using sodium bicarbonate as gas-forming agent and Chitosan, HPMC K4M and Ethyl cellulose as polymers. The preformulation parameters like Organoleptic properties, angle of repose, bulk density, tapped density, Hausners ratio, carrs index and compressibility index of pure drug was evaluated and complied with the pharmacopoeial specifications. FTIR studies showed there was no interaction between drug and polymer. The prepared tablets were evaluated in terms of their physical characteristics, post compression parameters in vitro release and buoyancy lag time the results of the in vitro release studies showed that the optimized formulation (C7) could sustain drug release for 12 hrs by using Ethyl cellulose in the concentration of 50 mg. The in vitro drug release followed Kors Mayer peppas release. Results revealed that the floating formulation of the Clarithromycin is the best formulation to obtain better therapeutic effect and Ethyl cellulose at a concentration of 50mg up to some extent it increases the Bioavailability of the drug to retain the dosage form on the desired site for effective period of the time.

Design, development and QbD based optimization of double coated spheronized aceclofenac pellets for effective palliative care in rheumatoid arthritis

ObjectiveDesign, develop, optimize and validate a chronotherapeutic double coated aceclofenac pellet formulation prepared using extrusion-spheronization technique for effective palliative action of RA symptoms. SignificanceRA is a chronic systemic autoimmune disease leading to pain in joints, connective/fibrous tissues, cartilages, ligaments, muscles and tendons. RA mostly prevails at productive age of human life and its chronic effect may lead to deformity or disability thereby resulting in substantial socioeconomic burden. Early morning circadian manifestations of symptoms in RA are due to night time activation of inflammatory responses. Chronotherapeutic double coated pellet formulation can deliver aceclofenac according to circadian rhythm of RA symptoms leading to effective palliative action. MethodsCore aceclofenac pellets were prepared and double coated with inner swellable HPMC and outer erodible ethylcellulose layers to achieve desired lag time in ACE release. Formulation and process parameters of double coating process were optimized by QbD approach. Drug release lag time, production yield and pellet morphology were identified as CQAs. ResultsIn vitro drug release and in vivo pharmacokinetic studies revealed that optimized pellet formulation with 15% weight gain due to swellable layer, 1.6% weight gain due to erodible layer and 5% of pore forming agent exhibited highest desirability indices with drug release lag time of 5h, production yield of 79 ± 2%, 1.05 ± 0.04 aspect ratio, 88.1% ± 1.25% roundness and.1.22 ± 0.2 mm pellet size. ConclusionDesired ACE release lag time required to match the circadian rhythm of RA was achieved through double coated spheronized pellets, without any associated drawback of dose dumping.

A REVIEW ON RECENT ADVANCEMENT IN PULSATILE DRUG DELIVERY SYSTEMS

Delivery systems with a pulsatile-release method are particularly involved in designing medicines for which traditional managed drug-release systems with the continuous release are not suitable. This medication also has a high first-pass impact or special conditions for chrono-pharmacology. These medications also have a high first-pass or unique chronopharmacological effect. The pulsatile release profile is characterised by a duration of no release (lag time) followed by a fast and full release of the drug. Pulsatile drug delivery systems may be classified into site-specific systems in which the drug is released inside the gastrointestinal system (e. g. colon) or time-controlled devices wherein the drug is released after a well-defined time period. Site-regulated release is typically controlled by environmental factors, such as pH or enzymes found in the intestinal tract, whereas drug release from time-controlled processes is controlled mainly by the delivery system and, preferably, not by the environment. This review covers various single-and multiple-unit oral pulsatile drug-delivery systems with an emphasis on time-controlled drug-release systems.

DESIGN AND DEVELOPMENT OF FLOATING PULSATILE DRUG DELIVERY OF LOSARTAN POTASSIUM

Objective: The objective of the present investigation was to the development of floating pulsatile drug delivery system of Losartan potassium (LP) tablets for obtaining no drug release during floating followed by pulsed, rapid drug release to achieve chronotherapeutic release. In hypertension, the risk of getting heart attacks early in the morning is high and therefore, there was need to develop drug delivery, which will release drugs at morning hours and provide efficacious therapy. LP is a short biological half-life (1.5-2.5h) and readily absorbed from the stomach and upper gastrointestinal tract.
 Methods: Tablet formulation was prepared by press coating of rapid release core tablets and core tablets were further top coated with a buoyant layer of HPMC K4M and sodium bicarbonate. Various grades of HPMC polymer (E5/E15/E50) were used for the pulsatile coating layer. The developed formulations were characterized for physical characteristics, floating lag time, floating time, release lag time, drug content, swelling index, in vitro dissolution studies, DSC and XRD.
 Results: The FTIR and DSC studies predicted that there was no chemical interaction between drug and excipients. The core tablet coated with HPMC E50 showed a high swelling index and release the drug 97.60±1.2% at 6h. Buoyant layer with 80 mg HPMC K4M and 25 mg sodium bicarbonate gave satisfactory floating lag time.
 Conclusion: The system showed an excellent lag phase followed by burst release in the distal small intestine, which gives site and time-specific delivery of LP acting as per chronotherapy for treatment of hypertension.

Preparation and Drug Release Mechanism of Time Controlled Explosive Pulsatile Tablets with Ethylcellulose Coating

Core tip: The development of pharmacology in the decade revealed the biological rhythm of the occurrence and development of certain diseases, usually the circadian rhythm. Therefore, chronopharmacological drug delivery is of great significance in the prevention and treatment of diseases having onset rhythm inconvenient to take drug. An easy-to-prepared, time-controlled explosive metoprolol tartaric pulsatile tablet was developed in order to provide patients with timed therapy of effective blood drug concentration at the optimal time. The formulation and process were optimized using single factor experiments and orthogonal experiments. In addition, the swelling and water absorption rate of tablet and the mechanical properties of the coating film were measured to further reveal its release mechanism. The results showed that the strong tensile strength of coating film and the weak flexibility of EC film resulted in a shell-type exploding rupture of the coating film followed by the pulsatile fast release of drug when the swelling force of core tablet caused by water uptake was high enough. Both the swelling capacity of core tablets and the thickness of coating film together controlled the lag time of drug release. The prepared time-controlled explosive pulsatile tablets with ethylcellulose coating thereafter are expected to be used for the delivery of therapeutic agents for chronotherapy by adjusting the lag time of drug release to match the different high attack rhythm of the exact diseases. Abstract: Background The time rhythm of human body is associated with the occurrence and development of many diseases, and it also affects the efficacy and pharmacokinetic characteristics of the corresponding therapeutic drugs. Therefore, the chronopharmacological drug delivery system has potential applications. Aim In this work, it is proposed to develop a kind of pulsatile release tablet of simple structure and preparing process, thus to provide an alternative drug delivery system for therapeutic agents used in treatment of diseases of typical onset biorhythm at period inconvenient to take drug. Methods Metoprolol tartrate (MT), a drug widely used clinically to treat cardiovascular diseases was selected as a model drug for developing pulsatile tablets of time-controlled explosive system (TES). The MT pulsatile tablets were ethyl cellulose (EC) coating tablets produced by pan coating process, and the core tablets were prepared by direct compression. The formulation and process was optimized by single factor test and orthogonal design. Also, the pulsatile release mechanism of the tablets was discussed through investigating the water absorption and swelling capacity of tablets as well as the mechanical properties of EC free film. Results A kind of pulsatile tablets of MT were developed with a drug release lag time around 7 h and a fast release of drug after lag time. When the swelling force of core tablet caused by water uptake was high enough over the tensile strength of EC coating film, the MT pulsatile tablets demonstrated a shell-type exploding rupture due to the great rigidity and weak flexibility of EC film, and then a fast pulsatile release of drug was observed. Both the swelling capacity of core tablet and the thickness of coating film together controlled the lag time of drug release. The lag time showed a good linear relationship with the thickness of coating film (r = 0.9984, P < 0.01). The sort and amount of fillers and disintegrants dominated the release behaviour after lag time. Conclusion The developed MT pulsatile tablets can exert a timely release of drug before peak onset period of hypertension and angina pectoris early in the morning after drug taking around 22:00 P.M the night before. The good linear relationship between lag time and coating thickness enabled the pulsatile tablets to be used for delivery of other therapeutic agents of similar chronotherapy demand by adjusting the coating thickness to achieve the appropriate lag time of drug release to match the different high attack rhythm of the exact diseases.

Drug Release and Pharmacokinetics Behavior of a Simple Ethylcellulose Coating Pulsatile Tablet of Time-Controlled Explosive System

Core tip: The time rhythm of the human body is associated with the occurrence and development of many diseases. Kinds of diseases of particular onset biorhythm provided the room for the development of chronopharmacological drug delivery systems. Metoprolol tartrate (MT), a medicine commonly used for treatment of cardiovascular diseases in clinic, was selected as model drug to develop a time-controlled explosive pulsatile tablet. The prepared MT pulsatile tablets showed a drug release lag time of 7.10 h in vitro perfectly consistent with the absorption lag time of 7.04 h in vivo , which ensured the pulsatile tablet a promising chronopharmacological drug delivery system for MT to prevent and treat the peak attack of hypertension and angina pectoris early in the morning. Abstract: Background The time rhythm of human body is associated with the occurrence and development of many diseases. Kinds of diseases of particular onset biorhythm provided the room for the development of chronopharmacological drug delivery systems. Aim In this work, the drug release and pharmacokinetics behavior of metoprolol tartrate (MT) pulsatile tablet developed in our lab was investigated to figure out its feasibility of convenient drug taking to exert effective chronotherapy for cardiovascular diseases like hypertension and angina pectoris. Methods The in vitro release behavior of MT pulsatile tablets was investigated by using basket method. The appearance and morphology of MT pulsatile tablets during drug release was observed by naked eye and scanning electronic microscope, respectively. In vivo pharmacokinetics performance was studied in New Zealand rabbits. Results The lag time of MT pulsatile tablets was approximately 7 h in vitro , and a fast release was observed thereafter, with more than 90% releasing within 10 min. The pharmacokinetics study in rabbits demonstrated a perfect consistence in the absorption lag time of 7.04 ± 0.29 h in vivo . Compared with the marketed conventional tablet, the MT pulsatile tablet showed a bioequivalence in absorption extent with a relative bioavailability of 110.04%, but not in absorption rate. Conclusion The designed lag time of 7 hours enabled the MT pulsatile tablets to achieve effective chronotherapy for cardiovascular diseases like hypertension and angina pectoris with a high attack rhythm around 4:00-6:00 A.M by giving medicine conveniently around 22:00 P.M. the night before.

Formulation and in vitro Characterization of Time Release Tablets of Propranolol Hydrochloride

The objective of this investigation was to prepare and evaluate propranolol hydrochloride time release tablets using press coating technique. The time release tablet consisted of two layers, a core tablet containing the active ingredient and an outer cell coating. The core tablet was prepared with the active ingredient using conventional method. Press coated optimized tablet was formulated using different ratios of ethyl cellulose and hydroxypropyl methylcellulose K4M. The coated tablets were evaluated by estimating the physical attributes, drug content, X-ray powder diffraction, Fourier-transform infrared spectroscopy and in vitro drug release profile. Based on the evaluation parameters formulation F10 showed a 6 h release lag time. The release pattern of F10 formulation fulfilled the circadian variation matching the chronotherapeutic objective of hypertension.

THE Formulation and In-vitro evaluation of press coated tablets of pravastatin for pulsatile drug delivery

The aim of present study is to formulate and evaluate Pravastatin pulsatile drug delivery system by press coated method to mimic the circadian rhythm of the disease by releasing the drug with a distinct predetermined lag time of 6 hrs. The basic design of the system consists of a rapid release core and controlled release coat. Core blend was evaluated for flow properties, hardness, thickness, friability and invitro drug release. Invitro drug release studies of press coated tablets for various formulations i.e., P1F6-P5F6 was conducted. From the results obtained by executed trails P5F6 of coated tablet containing 50% of ethyl cellulose and 20% of HPMC K15M concentration shows lag time up to 6hr and followed by complete drug release at the end of 8hr. Among these, P5F6 was considered as optimized formulation based on the lag time and percent of drug release (98.96% of drug release in 6 hrs). So, it is selected as optimized formulations for designing pulsatile device. Keywords: Pravastatin, SSG, lycoat, ethyl cellulose, HPMC K15M, pulsatile drug delivery, Press coated method.

PHARMACOKINETIC COMPARISON OF MONTELUKAST SODIUM FORMULATIONS AFTER A SINGLE ORAL DOSE IN HEALTHY GUINEA PIGS

Objective: Pharmacokinetic evaluation of montelukast sodium chronomodulated capsules (sustained-release solid dispersion of drug enclosed in pH-sensitive film-coated hard gelatin shell) and marketed tablets has been carried out in this study.&#x0D; Methods: A single oral dose of prepared capsules and marketed conventional tablets was administered in healthy male Dunkin-Hartley albino guinea pigs. Blood samples were collected at different time intervals and plasma concentration of drug was determined by reversed-phase high-performance liquid chromatography. Different pharmacokinetic parameters were assessed from plasma drug concentration-time profile by one-compartment model, first-order kinetics.&#x0D; Results: Pharmacokinetic parameters such as time to reach maximum concentration, elimination rate constant, elimination half-life, and mean residence time data indicates that drug release from chronomodulated capsules is significantly prolonged with initial release lag time of 3.5–4 h in comparison with marketed conventional tablets. However, maximum drug plasma concentration, area under the concentration-time curve, and apparent volume of distribution values show non-significant difference between capsules and marketed tablets.&#x0D; Conclusion: The findings specified that capsules were providing time controlled delivery of drug at a desired rate for prolonged time, which may be helpful for the prevention of episodic attack of asthma in early morning hours.

Semisolid-filled Capsules of Carvedilol for Improving Dissolution Behaviour

The present investigation was aimed at enhancing the dissolution properties of carvedilol, a poorly water-soluble drug using a combination of solid dispersion and semisolid-filled capsule. The use of lauroyl polyoxyl-6 glycerides as a carrier in a semisolid base to improve the dissolution behaviour of carvedilol was investigated. Solid dispersions containing carvedilol were prepared and percent drug content was assessed. In vitro dissolution studies, Fourier-transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy were used to characterize solid dispersions. Semisolid-filled capsules of carvedilol were prepared using different bases, and their percent drug content and in vitro dissolution behaviour were studied. The optimized solid dispersion containing 3 parts of poloxamer and 0.2 part of Plasdone K90 with respect to 1 part of carvedilol was incorporated into an optimized semisolid base containing 20 parts of lauroyl polyoxyl-6 glycerides with respect to 1 part of carvedilol). The combination of solid dispersions and semisolid-filled capsule produced a significant increase in the rate of release of the drug. The differential scanning calorimetry thermogram of the optimized semisolid formulation did not show carvedilol peak, which suggested that carvedilol had dissolved in the base in the presence of lauroyl polyoxyl-6 glycerides. The dissolution of carvedilol was improved and the lag time of drug release was reduced in the semisolid-filled capsules in which lauroyl polyoxyl-6 glycerides was used as a carrier.

Modification of alginate beads using gelatinized and ungelatinized arrowroot (Tacca leontopetaloides L. Kuntze) starch for drug delivery

Arrowroot (Tacca leontopetaloides L. Kuntze) starch in gelatinized and ungelatinized forms was used to modify the characteristics of calcium alginate (CA) beads containing diclofenac sodium (DS). Sodium alginate (SA) was able to molecularly interact with ungelatinized starch (UGS) granules and gelatinized starch (GS) gel via hydrogen bonding mechanisms in the dispersions, leading to viscosity synergism before cross-linking. The GS-CA beads provided a significantly higher DS entrapment efficiency than the UGS-CA beads. The added UGS retarded the water uptake of the CA beads, resulting in slower DS release profiles in purified water and a longer lag time of DS release in pH 6.8 phosphate buffer. On the other hand, GS enhanced water uptake and accelerated the DS release of the beads in both media. Moreover, the 1%GS-CA beads displayed slower DS release than the CA and 1%UGS-CA beads in pH 6.8 phosphate buffer when simulated gastro-intestinal (GI) condition was used. This study shows that UGS and GS obtained from Tacca leontopetaloides L. Kuntze have good potential to improve drug entrapment efficiency of the CA beads, and the DS-loaded GS-CA beads can be used as multiunit dosage forms for sustaining drug release in simulated GI condition.

Chronomodulated drug delivery system of Irbesartan: Formulation and development using Desing of Experiment (DoE)

The work is based on pulsatile principles to deliver a programmed dose of Irbesartan, an angiotensin-II receptor antagonist for chronotherapy of hypertension induced by excessive secretion of aldosterone, thereby lower the blood pressure at early morning. Solid dispersion of Irbesartan, a BCS class II drug, was prepared by using Poloxamer-188 by melt method in ratio of 1:1 to increase the dissolution properties of drug. Compressed coated pulsatile tablets included a core layer consisting of Kyron T-134 as a super-disintegrant and pulsatile layer comprising of HPMC K4M and Eudragit RLPO. The prepared core tablets were evaluated for weight variation, hardness, thickness, friability, drug content, disintegration time and In vitro dissolution studies. Final core tablet (C8) was selected on the basis of disintegration time (23.33 ± 2.08 s). For optimization Face centred central composite design was employed to study the effect of independent variables viz. Weight ratio of HPMC K4M: Eudragit RLPO (X1) and Total weight of coating (X2) on dependent variables viz. Drug release lag time (Y1) and Drug release after lag time within 15 min (D15) (Y2). Results revealed positive influence of independent factors on responses. The data were statistically analyzed using ANOVA and were found to be statistically significant (P < .05). Mathematical modeling for kinetic studies revealed that the release profile after lag time followed first order kinetics. Accelerated stability studies for one month at 40 ± 2 °C/75 ± 5% RH showed no remarkable changes concluding that a successful pulsatile drug delivery system of Irbesartan was developed.

In vitro and in vivo evaluation of controlled-release matrix tablets of highly water-soluble drug applying different mw polyethylene oxides (PEO) as retardants

The aim of the work presented is to prepare a controlled-release hydrophilic matrix tablet (CMT) controlling release of highly water-soluble drug applying pure combination of high- and low-Mw PEO as matrix materials, to avoid the lag time of drug release, and to overcome incomplete release in later stages. The influences of types and amounts of different Mw PEOs used, drug loading, pH of release medium and agitation rate on drug release were evaluated. The study of uptake and erosion of matrix was conducted and mechanism of improving drug release was discussed. In vivo pharmacokinetics of the CMT and reference preparation self-made controlled-release osmotic pump tablets (COPT) were performed in beagle dogs. The optimized formulation containing 43% PEO WSR 303 and 32% PEO N750 showed a zero order release from 1 h to 12 h. In vivo results demonstrated that the CMT had similar AUC0-48 h and Cmax with the COPT but smaller Tmax than the COPT and provided a more stable therapeutic concentration compared to the COPT. In conclusion, hydrophilic matrix tablet combining only different Mw PEOs as matrix materials had very good potential to be developed into a controlled-release drug delivery system for highly water-soluble drug. Besides, its manufacturing processes were succinct which would be preferable for modern medicine industry.

Early rising asexual parasitaemia in Nigerian children following a first dose of artemisinin-based combination treatments of falciparum malaria

BackgroundEarly rising asexual parasitaemia (ERAP), initially defined as ‘an increase in the parasite count over the baseline pre-treatment level during the first 24 h of treatment’ of falciparum malaria with artemisinin derivatives is well documented, but there is no characterization of its risk factors, kinetics, molecular features or relationship to late-appearing anaemia (LAA) in acute falciparum malaria in African children following oral artemisinin-based combination therapies (ACTs).MethodsERAP was defined as ≥5% increase in pre-treatment parasitaemia within 8 h of initiating treatment. Parasitaemia was quantified pre-treatment and 1–2 hourly for 8 h, and less frequently thereafter for 6 weeks following randomized treatment of acutely malarious children with artesunate-amodiaquine, artemether-lumefantrine or dihydroartemisinin-piperaquine. Risk factors were determined by stepwise multiple logistic regression model. Kinetics of release into and of elimination of asexual parasites and DNA clones from peripheral blood were evaluated by method of residuals and non-compartment model, respectively. Parasite population changes were evaluated morphologically and by molecular genotyping.ResultsERAP occurred in 205 of 416 children. A parasitaemia <100,000/μL and parasitaemia 1 day post-treatment initiation were independent predictors of ERAP. In children with ERAP: mean and peak time of increase in parasitaemia were 105.6% (95% CI 81–130.1) and 2.5 h (95% CI 2.2–2.7), respectively. Mean lag time, half-time and rate constant of release were 0.2 h (95% CI 0.2–0.3), 1 h (95% CI 0.9–1.1), and 0.9 h−1 (95% CI 0.8–1), respectively. Schizonts and young gametocytes were seen only in peripheral blood of few children with ERAP. In age-, gender-, baseline parasitaemia- and treatment-matched children with and without ERAP, parasite DNA clearance time and area under curve of number of DNA clones versus time were significantly higher in children with ERAP indicating peripheral retention of released parasites followed by elimination. DNA clone elimination was monoexponential.ConclusionERAP is common, occurs rapidly as first order process and may be due to mobilization of parasites from deep tissue following a first dose of ACTs of acute childhood falciparum malaria.Trials registrationPan African Clinical Trial Registry PACTR201508001188143, 3 July 2015; PACTR201510001189370, 3 July 2015; PACTR201508001191898, 7 July 2015 and PACTR201508001193368, 8 July 2015.

Development and Evaluation of Sustain Release Simvastatin Pellets

The aim of the present study is to develop and evaluate sustained release simvastatin pellets for the treatment of hyperlipidemia. This disease directly depends upon circadian rhythm of the body i.e. the maximal cholesterol synthesis is generally higher during the night. The activity of rate limiting enzyme HMG-CoA reductase is higher in the night time. Simvastatin an HMG CoA reductase inhibitor requires frequent dosing due to the lower bioavailability and shorter half life. The sustain release simvastatin pellets can be taken before bed time and capable of releasing drug after predetermined lag time. Simvatstain pellets were developed by the extrusion spheronization technique. The simvastatin pellets were prepared by using blend of microcrystalline cellulose (MCC), lactose, crospovidone and polyvinyl pyrrolidone (PVP K-30). The process variables such as spheronizing speed, amount of spheronizing aid (MCC) and binder (PVP K-30) were optimized and reported. The obtained pellets were subjected for determination of percentage yield, hardness, physicochemical properties and particle size analysis. The prepared pellets were further coated with ethyl cellulose as release rate retardant polymer, using fluidised bed processor by Wurster technique. Increasing the level of the ethyl cellulose coating retarded the water uptake and thus prolong the lag time for release of drug. The 30 % ethyl cellulose coating gave least release in 0.1 N HCl containing 0.5% SLS in 2 hours, in next four hours 97.4 % release was observed in Phosphate buffer.

Pectin/HPMC dry powder coating formulations for colon specific targeting tablets of metronidazole

The objective of this study was to develop a dry powder coating technique applied to colon targeting tablets containing metronidazole (MET) by using a pan coater. The coating formulation consisted of a polymer mixture (pectin/HPMC) and plasticizer (dibutyl phthalate). Dissolution rate of MET was conducted at pH 1.2, 7.4 and 6.8 in the presence of pectinolytic enzyme. The lag time release of MET was simultaneously controlled by enzyme signal in colonic medium and coating level. There was a significant correlation between the coating level and lag time release when the ratio of pectin: HPMC was from 1:1 to 3:1. SEM indicated a homogenous coating layer when coated tablets were cured at 100 °C. The lag time phase of drug release was prolonged one more hour when curing time increased from 24 to 72 h at 60 °C. The in-vitro lag time of optimal formulation was 6.01 h. The X-ray imaging study showed the presence of coated tablets in ascending and descending colon after 6 and 8 h of tablet administration, respectively. The obtained dry powder coating technique had potential to prepare pulsatile release systems with long lag time release and without using organic solvent.

3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics.

Three dimensional printing (3D printing) was used to fabricate novel oral drug delivery devices with specialized design configurations. Each device was loaded with multiple actives, with the intent of applying this process to the production of personalized medicines tailored at the point of dispensing or use. A filament extruder was used to obtain drug-loaded--paracetamol (acetaminophen) or caffeine--filaments of poly(vinyl alcohol) with characteristics suitable for use in fused-deposition modeling 3D printing. A multinozzle 3D printer enabled fabrication of capsule-shaped solid devices containing the drug with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different to the drug in the adjacent layers, and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least-squares component matching to produce false color representations of distribution of the drugs was used. This clearly showed a definitive separation between the drug layers of paracetamol and caffeine. Drug release tests in biorelevant bicarbonate media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both paracetamol and caffeine was simultaneous and independent of drug solubility. With the DuoCaplet design, it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device; the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design configurations and unique drug release characteristics, which would not otherwise be possible using conventional manufacturing methods.

Applicability of Gum Karaya in the Preparation and &lt;I&gt;in Vitro&lt;/I&gt; Evaluation of Losartan Potassium as Chronotherapeutic Drug Delivery System

The objective of this investigation is to study the applicability of gum karaya, the natural gum for the preparation and in vitro evaluation of losartan potassium, as Chronotherapeutic Drug Delivery System (ChDDS). The compression-coated timed-release tablets (CCT) containing losartan potassium in the core tablet were prepared by dry coating technique with different ratios of gum karaya as the outer coat. The parameters investigated were tensile strength, friability, in vitro dissolution studies and drug concentration. The optimized formulation was further characterized by powder XRD and FTIR to investigate interactions and no interactions observed. The tensile strength and friability of all the CCT were between 1.06-1.23 MN/m2 and &lt; 0.3% respectively. All the CCT showed a clear lag time before a burst release of drug. However, the lag time of drug release increased as the amount of gum karaya in the outer layer increased. For instance, the lag time of LGK1, LGK2, LGK3, LGK4, LGK5, LGK6 and LGK7 were 16, 10.5, 5.5, 3, 2, 1.5 and 0.5 hrs respectively. The drug content of all the CCT was &gt;98%. Formulation LGK3 was taken as an optimized formulation which can be exploited to achieve ChDDS of losartan potassium for the treatment of hypertension.