Oral Controlled Release Dosage Forms Research Articles

A Recent Update on Formulation and Development of Gastro-Retentive Drug Delivery Systems

Oral route has been the most convenient and accepted route of drug delivery. Owing to tremendous curative benefits of the oral controlled release dosage forms are being preferred as the interesting topic in pharmaceutical field to achieved improved therapeutics advantages. Gastro retentive drug delivery system is novel drug delivery systems which has an upper hand owing to its ability of prolonged retaining ability in the stomach and thereby increase gastric residence time of drugs and also improves bioavailability of drugs. Concept of novel drug delivery system arose to overcome the certain aspect related to physicochemical properties of drug molecule and the related formulations. In this context, various gastro retentive drug delivery systems have been used to improve the therapeutic efficacy of drugs that have a narrow absorption window, are unstable at alkaline pH, are soluble in acidic conditions, and are active locally in the stomach. Concept of novel drug delivery system arose to overcome the certain aspect related to physicochemical properties of drug molecule and the related formulations. Various approaches are currently used including gastro retentive floating drug delivery systems, swelling and expanding system, polymeric bio adhesive systems, modified shape systems, high density system and other delayed gastric emptying devices. Moreover, future perspectives on this technology are discussed to minimize the gastric emptying rate in both the fasted and fed states. The present review briefly addresses the physiology of the gastric emptying process with respect to floating drug delivery systems. The purpose of this review is to bring together the recent literature with respect to the method of preparation, and various parameters affecting the performance and characterization of floating microspheres. Attempt has been made to summarize important factors controlling gastro retentive drug delivery systems. Overall, this review may inform and guide formulation scientists in designing the gastro retentive drug delivery system.

Plantago Ovata and Locust Bean Gum as a Natural Polymer in Hydrodynamically Balanced Systems: A Review

Hydrodynamically Balanced systems have wide development as they have achieved the parameters of modern drug delivery system, it is a type of system which owes very tremendous and curative benefits for the delivery of oral controlled release dosage forms and have wide properties in many aspects such as its main role is to maintain the effective concentration in the system for longer period of time. To reduce the gastric mucosal irritation due to the presence of synthetic polymers, being a natural polymer incorporation of Plantago ovate (Psyllium Husk) could ease out the mucosal irritation in the gastric region. Due to its properties such as a rate-controlling polymer possessing a very good quality of swelling and good gelling nature, and also incorporated as a matrix-forming agent basically in the modified release formulation. Locust bean gum can be used as sustained-release carriers and release modifiers for the delivery of drugs. It is a neutral plant galactomannan extracted from the seeds (kernels) of the carob tree Ceratonia siliqua L fabaceae. Nowadays it is focussing polymer and a lot of researchers are focussing on exploring the potential in topical drug delivery, colonic drug delivery, oral sustained drug delivery, ocular drug delivery, buccal drug delivery.

Araucaria Gum: Novel Natural Polymer for Controlled Drug Delivery. Development, In Vitro and In Vivo Evaluation of Araucaria Gum Based Matrix Tablets for Controlled Release.

Assessment of natural polymers in oral controlled drug delivery. The objective of the present investigation was to assess of Araucaria gum (AHG) obtained from bark exudates of the Araucaria heterophylla (family: Araucariaceae) for the design of oral controlled release forms, in particular tablet dosage forms by using matrix systems. Diclofenac sodium was used as model drug and compared with the marketed formulation. Matrix tablets were prepared by wet granulation technique and 5% w/v of AHG dispersion water was used as granulating agent for preparation of AHG matrix tablets. AHD2 (3:20) was found to be the optimized formulation based on in vitro drug dissolution studies. FTIR and DSC studies performed on the optimized formulations indicated no drug-polymer interaction. AHD2 (3:20) was found to be stable after accelerated stability testing for 6 months as per ICH guidelines. Pharmacokinetic studies of the optimized formulation were performed in healthy Albino Wister rabbits in comparison with that of the pure drug by estimating pharmacokinetic parameters and mean residence time (MRT). It was found that there is a significant increase in the bioavailability of diclofenac sodium from AHD2 formulation which was evident from the high AUC and MRT values compared with the pure drug. The above results clearly indicated that AHG gum can be used for the development of oral controlled release dosage forms by using matrix systems.

IONOTROPIC TRAPPING LECITHIN BASED CILOSTAZOL NANOCOCHLEATES FOR DRUG DELIVERY APPLICATIONS

The nanocochleate drug delivery is based on encapsulating drugs in multilayered lipid crystal matrix (a cochleate) to potentially deliver the drug safely and effectively through the lipoidal membrane. Cilostazol is approved for the treatment of intermittent claudication and used as fibrinolytic agent, platelet aggregation inhibitor, bronchodilator agent, phosphodiesterase III Inhibitor and vasodilator agent. therefore, this drug delivery is suitable to deliver drug molecules into blood vessels. Formulations with lecithin showed good in vitro drug release, drug entrapment study results and the drug in formulations was found to be intact and compatible with lipids used. Two optimized formulations containing cilostazol lecithin-cholesterol showed Korsemayer peppas model perfect zero order release and showed better sustained and controlled drug release. Lecithin-cholesterol nanocochleates prepared by external ionotropic trapping method was found to be better ionic cross linking of drug-lipids particles. Therefore, ionotropic cross-linked particles are promising carriers for oral controlled release dosage forms.

INSIGHT IN TO APPLICATIONS OF THERMAL SINTERING TECHNIQUE IN NDDS SPECIALLY GRDDS

Oral route the most popular route of administration for systemic action .Oral conventional drug delivery has following limitation of unpredictable gastric emptying rate, short gastro intestinal transit time, and inter subject variability leads in to less bioavailability so goal of drug delivery were not properly achieved by conventional dosage forms. So there is need of sustained drug delivery. The sustained drug delivery can be achieved by matrix tablet wherein a solid drug is dispersed in an insoluble matrix. The matrix tablets can be prepared by wet granulation method or modern thermal sintering technique. Sintering concept in the pharmaceuticals technology is very novel. The term sintering means fusion of particles or formation of welded bonds between particles of polymer. Sintering is a method of heating the material in a sintering furnace below its melting point (solid-state sintering) until its particles adhere to each other. In this process, polymer particles undergo fusion or formation of welded bonds between the each particle. Controlled release oral dosage forms were developed by sintering the polymer matrix to its glass transition temperature. The use of sintering technique adds to the effectiveness of polymers to extend the release of drug from formulation depending upon the duration and temperature of sintering. Sintering technique enhanced the extent of drug retardation from the systems studied is short enough for it to be a suitable candidate for SR formulation. The term sintering means fusion of particles or formation of welded bonds between particles of polymer. The SR oral dosage forms can be developed by sintering the polymer Gastroretentive drug delivery system is facing many challenges which can be overcome by upcoming newly sintered technique.  This review article explains about various aspects of sintering technique also highlighted some research work on sintered technology. Keywords: Oral route, sintering, sustain, thermal, drug delivery, research workÂ

Evaluation of the drug solubility and rush ageing on drug release performance of various model drugs from the modified release polyethylene oxide matrix tablets

Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers for the manufacture of tablets stored at 40 °C. The results of the present study suggest that the drug release from the matrix was affected by the length of storage conditions, solubility of drugs and the molecular weight of the polymers. Generally, increased drug release rates were prevalent in soluble drug formulations (propranolol) when stored at the elevated temperature (40 °C). In contrast, it was not observed with semi soluble (theophylline) and poorly soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This indicates that the main parameters controlling the drug release from fresh polyox matrices are the solubility of the drug in the dissolution medium and the molecular weight of the polymer. DSC traces indicated that that there was a big difference in the enthalpy and melting points of fresh and aged PEO samples containing propranolol, whereas the melting point of the aged polyox samples containing theophylline and zonisamide was unaffected.Graphical abstractᅟ

Controlled-release oral dosage forms containing nimodipine solid dispersion and hydrophilic carriers

The aim of this study was to prepare solid dispersion of nimodipine (NMD) by solvent evaporation method to overcome the poor water solubility of NMD, and to formulate controlled-release (CR) tablets containing the NMD solid dispersion. NMD is a dihydropyridine calcium-channel antagonist that is practically insoluble in water. Owing to the short half-life of the drug in the plasma, NMD immediate-release tablets should be administered frequently for the treatment and prevention of ischemic disorders following aneurysmal subarachnoid hemorrhage. In this study, solid dispersion technique was applied to increase the low solubility of NMD. Carriers for solid dispersions were prepared with different kinds of hydrophilic polymers. Kinetic solubility studies were performed for the prepared solid dispersions, using sodium acetate buffer (pH 4.5). Solid dispersions were then characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectrometry (FT-IR). CR tablets containing the NMD-PVP K30 solid dispersions were designed to reduce the dosing interval and increase patient compliance. Hydroxypropyl methylcelluloses (HPMC) were used as release-modifiers, and lactose anhydrous as a diluent.

Pharmacoscintigraphy studies to assess the feasibility of a controlled release formulation of ziprasidone

Ziprasidone, like many BCS Class II drugs with low intrinsic solubility and a strong tendency to crystallize from supersaturated solutions, presents significant technical challenges when developing an oral controlled release dosage form. In order to achieve acceptable bioavailability and prolonged exposures for once-daily dosing, good colonic absorption and a reliable controlled release (CR) technology are necessary. To this end, a novel solubilized drug form— coated crystals made by spray drying (CCSD), was formulated and progressed into human clinical studies. This report describes studies of colonic absorption for the CCSD using the Enterion™ capsule and a pharmacoscintigraphy study in which the CCSD was orally administered via a radiolabelled osmotic tablet formulation. These studies demonstrated that the probability of achieving the required drug solubilization in the colon with the CCSD concept and thereby the desired once daily pharmacokinetic profile was extremely low.

Designing polymeric microparticulate drug delivery system for hydrophobic drug quercetin

The aim of this study was to investigate pharmaceutical potentialities of a polymeric microparticulate drug delivery system for modulating the drug profile of poorly water-soluble quercetin. In this research work two cost effective polymers sodium alginate and chitosan were used for entrapping the model drug quercetin through ionic cross linking method. In vitro drug release, swelling index, drug entrapment efficiency, Fourier Transforms Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and Differential Scanning Calorimetric (DSC) studies were also done for physicochemical characterization of the formulations. Swelling index and drug release study were done at a pH of 1.2, 6.8 and 7.4 to evaluate the GI mimetic action which entails that the swelling and release of the all the Formulation1 (F1), Formulation2 (F2) and Formulation3 (F3) at pH 1.2 were minimal confirming the prevention of drug release in the acidic environment of stomach. Comparatively more sustained release was seen from the formulations F2 & F3 at pH 6.8 and pH 7.4 after 7h of drug release profiling. Drug entrapment efficiency of the formulations shows in F1 (D:C:A=2:5:30) was approximately 70% whereas the increase in chitosan concentration in F2 (D:C:A=2:10:30) has shown an entrapment efficiency of 81%. But the comparative further increase of chitosan concentration in F3 (D:C:A=2:15:30) has shown a entrapment of 80% which is not having any remarkable difference from F2. The FTIR analysis of drug, polymers and the formulations indicated the compatibility of the drug with the polymers. The smoothness of microspheres in F2 & F3 was confirmed by Scanning Electron Microscopy (SEM). However F1 microsphere has shown more irregular shape comparatively. The DSC studies indicated the absence of drug-polymer interaction in the microspheres. Our XRD studies have revealed that when pure drug exhibits crystalline structure with less dissolution profile, formulated microparticles can help us to obtain amorphous form of the same drug that is likely to have more dissolution property. The findings of the study suggest that the microsphere formulations were a promising carrier for quercetin delivery and can be considered as a favorable oral controlled release dosage form for hydrophobic drug quercetin.

REVIEW ARTICLE CHITOSAN MICROSPHERES AS POTENTIAL CARRIERS FOR COLON TARGETING

Chitosan microspheres have been in the focus of increasing interest as polymeric drug carriers due to their appealing properties such as biocompatibility, biodegradability, low toxicity, mucoadhesion and relatively low cost of production. Gel formation can be obtained by interactions of chitosan with low molecular weight counter-ions such as polyphosphates. However, one drawback of using this natural polysaccharide for oral controlled release dosage forms is its fast dissolution rate in the stomach. Since chitosan is positively charged at low pH values (below its pKa value), it spontaneously associates with polyanions to form polyelectrolyte complexes (PEC). These PEC exhibit favorable physicochemical properties with preservation of chitosan's biocompatible characteristics. These complexes are therefore good candidates for the design of colon-targeted dosage forms. Various techniques are used for preparing chitosan microspheres which have been reviewed. This review also includes factors that affect the release characteristics of drugs from chitosan microspheres.

PATENTED PHARMACEUTICAL ORAL CONTROLLED RELEASE MATRIX SYSTEM

Abstrac t Oral controlled release drug delivery system becomes a very promising approach for those drugs that are given orally but having the high dosing frequency and shorter half - life. Matrix tablets serves as an important tool for oral controlled release dosage forms. Problems like patient compliance, drug targeting, local side effects, frequent administration and fluctuations in blood concentration levels, associated with their counterparts, the conventional dosage forms were rectified. Many of the pharmaceutic al dosage form are formulated as sustained release dosage form to retard the release of a therapeutic agent such that its appearance in the systemic circulation is prolonged and its plasma profile is sustained in duration. Tablets offer the lowest cost app roach to controlled and sustained release dosage forms. Matrix tablet as controlled release has given a new breakthrough for novel drug delivery system in the field of pharmaceutical technology. This review focuses on the various types of matrix systems ba sed on polymer used and porosity of matrix system i.e. hydrophilic, hydrophobic, fat wax, porous, non - porous, pH sensitive. An effort has been made to consolidate different types of patents granted across the globe for last thirty years in the field of mat rix system viz. tablet, pellets etc.

Tailoring controlled-release oral dosage forms by combining inkjet and flexographic printing techniques

We combined conventional inkjet printing technology with flexographic printing to fabricate drug delivery systems with accurate doses and tailored drug release. Riboflavin sodium phosphate (RSP) and propranolol hydrochloride (PH) were used as water-soluble model drugs. Three different paper substrates: A (uncoated woodfree paper), B (triple-coated inkjet paper) and C (double-coated sheet fed offset paper) were used as porous model carriers for drug delivery. Active pharmaceutical ingredient (API) containing solutions were printed onto 1cm×1cm substrate areas using an inkjet printer. The printed APIs were coated with water insoluble polymeric films of different thickness using flexographic printing. All substrates were characterized with respect to wettability, surface roughness, air permeability, and cell toxicity. In addition, content uniformity and release profiles of the produced solid dosage forms before and after coating were studied. The substrates were nontoxic for the human cell line assayed. Substrate B was smoothest and least porous. The properties of substrates B and C were similar, whereas those of substrate A differed significantly from those of B, C. The release kinetics of both printed APIs was slowest from substrate B before and after coating with the water insoluble polymer film, following by substrate C, whereas substrate A showed the fastest release. The release rate decreased with increasing polymer coating film thickness. The printed solid dosage forms showed excellent content uniformity. So, combining the two printing technologies allowed fabricating controlled-release oral dosage forms that are challenging to produce using a single technique. The approach opens up new perspectives in the manufacture of flexible doses and tailored drug-delivery systems.

Treatment of Chronic Pain in Older People

In the treatment of chronic malignant and non-malignant pain, opioids are used as strong analgesics. Frail elderly patients often have multiple co-morbidities and use multiple medicines, leading to an increased risk of clinically relevant drug-drug and drug-disease interactions. Age-related changes and increased frailty may lead to a less predictable drug response, increased drug sensitivity, and potential harmful drug effects. As a result, physicians face a complex task in prescribing medication to elderly patients. In this review, the appropriateness of the strong-acting opioids buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone and tapentadol is determined for use in elderly patients. Evidence-based recommendations for prescribing strong opioids to the frail elderly are presented. A literature search was performed for all individual drugs, using a validated and published set of 23 criteria concerning effectiveness, safety, pharmacokinetics and pharmacodynamics, experience, and convenience in elderly patients. First, information on the criteria was obtained from pharmaceutical reference books and a MEDLINE search. The information obtained on the individual drugs in the class of opioids was compared with the reference drug morphine. Evidence-based recommendations were formulated on the basis of the pros and cons for the frail elderly. Using the set of 23 criteria, no differentiation can be made between the appropriateness of buprenorphine, fentanyl, hydromorphone, morphine and oxycodone for use in elderly patients. Methadone has strong negative considerations in the treatment of chronic pain in the frail elderly. Methadone has a high drug-drug interaction potential and is associated with prolongation of the QT interval and a potential risk of accumulation due to a long elimination half-life. In addition, methadone is difficult to titrate because of its large inter-individual variability in pharmacokinetics, particularly in the frail elderly. Because of a lack of empiric knowledge, the use of tapentadol is not recommended in frail elderly persons. Nevertheless, tapentadol may prove to be a useful analgesic for the treatment of chronic pain in frail elderly persons because of its possible better gastrointestinal tolerability. In the treatment of chronic pain in the frail elderly, the opioids of first choice are buprenorphine, fentanyl, hydromorphone, morphine and oxycodone. In order to improve the convenience for elderly patients, the controlled-release oral dosage forms and transdermal formulations are preferred.

Treatment of Chronic Pain in Older People

In the treatment of chronic malignant and non-malignant pain, opioids are used as strong analgesics. Frail elderly patients often have multiple comorbidities and use multiple medicines, leading to an increased risk of clinically relevant drug-drug and drug-disease interactions. Age-related changes and increased frailty may lead to a less predictable drug response, increased drug sensitivity, and potential harmful drug effects. As a result, physicians face a complex task in prescribing medication to elderly patients. In this review, the appropriateness of the strong-acting opioids buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone and tapentadol is determined for use in elderly patients. Evidence-based recommendations for prescribing strong opioids to the frail elderly are presented. A literature search was performed for all individual drugs, using a validated and published set of 23 criteria concerning effectiveness, safety, pharmacokinetics and pharmacodynamics, experience, and convenience in elderly patients. First, information on the criteria was obtained from pharmaceutical reference books and a MEDLINE search. The information obtained on the individual drugs in the class of opioids was compared with the reference drug morphine. Evidence-based recommendations were formulated on the basis of the pros and cons for the frail elderly. Using the set of 23 criteria, no differentiation can be made between the appropriateness of buprenorphine, fentanyl, hydromorphone, morphine and oxycodone for use in elderly patients. Methadone has strong negative considerations in the treatment of chronic pain in the frail elderly. Methadone has a high drug-drug interaction potential and is associated with prolongation of the QT interval and a potential risk of accumulation due to a long elimination half-life. In addition, methadone is difficult to titrate because of its large inter-individual variability in pharmacokinetics, particularly in the frail elderly. Because of a lack of empiric knowledge, the use of tapentadol is not recommended in frail elderly persons. Nevertheless, tapentadol may prove to be a useful analgesic for the treatment of chronic pain in frail elderly persons because of its possible better gastrointestinal tolerability. In the treatment of chronic pain in the frail elderly, the opioids of first choice are buprenorphine, fentanyl, hydromorphone, morphine and oxycodone. In order to improve the convenience for elderly patients, the controlled-release oral dosage forms and transdermal formulations are preferred.

Controlled release of a highly hydrophilic API from lipid microspheres obtained by prilling: Analysis of drug and water diffusion processes with X-ray-based methods

This study deals with the development of an oral controlled-release dosage form of a highly water-soluble antiepileptic drug. In this respect, drug-loaded spheroid particles close to 380μm in diameter and composed of lipid binders were prepared by prilling. The purpose here was to thoroughly characterize the controlled-release mechanism of the drug in aqueous pH-6.8 buffered dissolution medium. Water and drug diffusion pathways as well as related kinetic parameters were determined by theoretical analysis of experimental data. Conventional in-vitro experiments performed by analytical high performance liquid chromatography showed that the released fraction reaches 90wt.% only after a 24-hour immersion in the dissolution medium, pointing out an effective sustained release mechanism. Interpretation of these data was strengthened by the implementation of an innovative methodology involving X-ray diffraction and microtomography to follow the structural evolution of the drug-loaded microspheres at molecular and microscopic scales. This approach allowed to explicit that water and drug transports obey to Fickian diffusion behaviours in good agreement with Crank's and non-simplified Higuchi's equations, respectively. In the latter case, independent modelling of drug release assimilating the microspheres to a variable-geometry reservoir was considered to refine the kinetic analysis of the diffusion process. The water diffusion coefficient Dw was found equal to 6.3×10−9cm2/s and the API apparent diffusion coefficient reduced to the tortuosity of the matrix DAPI/τ equal to 2×10−9cm2/s. This study ranks among the rare examples of monolithic dispersion device constituted by a highly soluble drug incorporated inside a perfectly inert lipid matrix. The dissolution liquid penetrates the particles through channels progressively created by the solubilization of the drug itself which occurs instantaneously at the inner front of the liquid.

Formulation and In Vitro Evaluation of Rifampicin Loaded Porous Microspheres

Rifampicin (RIF) is a major component in fixed dose combination therapy for the treatment of tuberculosis. RIF has low solubility and high permeability with high dose and hence it is classified as class II drug in Biopharmaceutical Classification System (BCS). RIF has poor and variable bioavailability because of its poor solubility, acid decomposition and, drug and food interaction. The present investigation was aimed to develop RIF loaded porous microspheres as a controlled release dosage form. Eudragit based porous microspheres of RIF were prepared by emulsion solvent diffusion method. Prepared porous microspheres were evaluated for its entrapment efficacy, morphology, thermal behavior, crystalline nature, in-vitro drug release and stability in simulated gastric fluid. The entrapment efficacy of drug loaded microspheres was found to be in the range of 19.04–74.57%. Surface morphology revealed the porous and spherical structure of microspheres. Differential scanning calorimetric studies confirmed that formulation process altered the crystalline nature of RIF. In vitro drug release studies indicated that drug to polymer ratio of 2:1 showed more than 85% drug release over the period of 3 h. Stability studies in simulated gastric fluid (SGF) indicated that low relative decomposition of 18.5% was achieved with high drug to low polymer ratio of 1:4. The results obtained from the present investigation concluded that RIF loaded porous microspheres are suitable for developing oral controlled release dosage form of RIF that can prevent acid decomposition and provide better biopharmaceutical properties. Further more the microspheres can be evaluated for preventing the interaction with isoniazid, other drugs and foodstuffs.

FORMULATION AND EVALUATION OF KETOPROFEN CELLULOSE ACETATE MICROCAPSULES

Ketoprofen is a potent non-steroidal anti-inflammatory,analgesic, and antipyretic drug used for treatment of variousrheumatic diseases and painful conditions. It is rapidly absorbedregardless the route of administration. Its half life is only 1-2 hrsafter oral administration. The aim of this work was to formulatesome controlled release oral dosage forms containing ketoprofen.Cellulose acetate was chosen for this purpose. Ketoprofen-celluloseacetate microcapsules were prepared by solvent evaporationtechnique. Polyvinyl alcohol was used as an emulsifier. Theprepared microcapsules were evaluated in terms of their releaseand surface characteristics. Also, the anti-inflammatory activity ofketoprofen was evaluated using the carrageenan-induced rat's pawedema method. The release of ketoprofen from the microcapsuleswas pH dependant and decreased by increasing the polymercontent and by increasing the organic phase volume. The particlesize of the produced microcapsules was decreased by increasingthe volume of organic phase, whereas it was increased byincreasing the polymer content. In conclusion, these resultssuggested that microencapsulation of ketoprofen using celluloseacetate could be a useful approach for controlled release of thedrug.

In vitro and in vivo evaluation of ranitidine hydrochloride ethyl cellulose floating microparticles

The real issue in the development of oral controlled release dosage forms is not just to prolong the delivery of drugs but also to prolong the presence of dosage forms in the stomach in order to improve the bioavailability of drugs with a ‘narrow absorption window’. In the present study, an anti-ulcer drug, ranitidine hydrochloride, is delivered through a gastroretentive ethyl cellulose-based microparticulate system capable of floating on simulated gastric fluid for > 12 h. Preparation of microparticles is done by solvent evaporation technique with modification by using an ethanol co-solvent system. The formulated microspheres were free flowing with good packability and encapsulation efficiencies were up to 96%. Scanning electron microscopy confirmed porous, spherical particles in the size range 300–750 µm. Microspheres showed excellent buoyancy and a biphasic controlled release pattern with 12 h. In vivo bioavailability studies performed on rabbits and Tmax, Cmax, AUC were calculated and confirmed significant improvement in bioavailability. The data obtained thus suggests that a microparticulate floating delivery system can be successfully designed to give controlled drug delivery, improved oral bioavailability and many other desirable characteristics.

Calculation of the antibiotic level in the lung tissue and bronchial secretion with an oral controlled-release dosage form

The drug level-time history in plasma and lung tissue was calculated with an antibiotic orally delivered in either an immediate-release or a controlled-release dosage form. The drug profiles were compared with experiment results given in the literature. In the same way, the drug level was evaluated in the bronchial secretion in contact with lung tissue. A numerical model, based on finite differences taking all the known facts into account was built and tested with the data found in the literature. Transport of the drug was looked at, including a stage of diffusion through the thickness of the lung tissue and a stage of convection into the bronchial secretion. A few parameters were thus considered, including the thickness of the lung tissue and the diffusivity of the antiobiotic through the tissue, the thickness of the bronchial secretion and the coefficient of convective transport into the sputum which characterizes its viscosity. Two partition factors were also introduced for the drug: between the tissue and the serum and between the lung tissue and the bronchial secretion.

Gastric Retentive Drug-Delivery Systems

The development of a long-term oral controlled-release dosage form has been difficult mainly because of the transit of the dosage form through the gastrointestinal (GI) tract. Several approaches to extend gastric residence time have been tried. The most commonly used systems are (1) intragastric floating systems, (2) high-density systems, (3) mucoadhesive systems, (4) magnetic systems, (5) unfoldable, extendible, or swellable systems, and (6) superporous hydrogel systems. The concept of each approach is examined, and improvements that are needed for further development are discussed. Background materials in the GI physiology that are necessary for understanding the concept and usefulness of each approach are also provided.