Stomach-specific Drug Delivery Research Articles

Development and Evaluation of In-Situ Floating Gel In treatment of Gastroesophageal Reflux Disease (Gerd)

Gastroretentive drug delivery systems can deliver narrow-window drugs to the upper stomach at a controlled rate. The raft forming process is better than floating structures, liquid dosing mediums, and in situ gelation for sustained drug release in the upper GI tract. According to statistics, lafutidine is exactly put in the parietal cells of the stomach mucosa, where the upper gastro-intestinal tract absorbs it. Lafutidine capsules had 65–70% bioavailability compared to intravenous infusion. Stability and absorption are acceptable between 1 and 4. The colon and lower gastrointestinal tract degenerate. In this study, the formulations were changed into gel for simulated gastric fluid (pH 1.2) and floated in the gastrointestinal environment, releasing medication for 12 hours. The finished device was tested. UV was linear from 5–30 g/ml with a regression value of 0.999. IR and DSC demonstrated negligible interaction between chemical, polymers, and excipients. Gelling polymers and calcium chloride were complexed with two xyloglucan polymers, gellan gum, and in situ gelling formulations. Xyloglucan was the best polymer for rheological tests, medication content, mucoadhesive strength, and gel strength. Lafutidine's solution formulae X10 and G10 did not improve in appearance, drug content, or dissolving profile after three months at 40°C and 75% RH. Wistar rats tested the in situ optimized Lafutidine gelling (X10, G10) formula. The ulcer index, stomach acid volume (ml), acidity (mEq / l / g), and pH were significantly affected by a single-way ANOVA solution and Tucky's multiples comparison test. The current work successfully developed, tested, and produced an oral continuous release floating Lafutidine gelling device with stomach-specific drug delivery, maintaining drug release and gastric preservation for the required time.

Central Composite Design Screened Mastic Gum Abetted Mucoadhesive Microspheres of Amoxicillin Trihydrate for Exterminating H. pylori

Aim: Searching for a new polymer that can be used in pharmaceutical formulation is a laborious and cost oriented practice. To resolve this, researchers are in search of a cost-effective and reliable excipient. Synthetic polymers are costly, whereas natural ones are abundant and economical. In the same way, discovering a new drug is a horrendous process with time, cost, and approval. The study's goal is to investigate Mastic gum's mucoadhesive properties by incorporating it into mucoadhesive microspheres with Amoxicillin trihydrate as a model drug. Methods: Nine interpretations of mucoadhesive microspheres were made with carbomer 934P and varying proportions of mastic gum (MG). A central composite design with design expert software is used to check the impact of independent variables (mastic gum and carbomer 934 P levels) on entrapment efficacy and mucoadhesion time as the responses. As part of congeniality studies, the microspheres were examined for amoxicillin trihydrate (ATH) content and liberation. Results: Good quality microspheres were formed that showed suitability with the excipients and possessed appreciable outcomes for the tests conducted. The study expressed the equation for ATH entrapment as +82.70+0.1333A+6.40B+0.0500AB+ 0.0000A₂-2.80B₂ and the mucoadhesion time as +13.10+0.2500A+1.42B-0.0500AB+0.1500A₂+0.1500B₂. These equations indicate the impact of independent variables on the response studies. These equations discovered that ATH entrapment increased with an increase in MG levels in the formulations and that the mucoadhesion time was greater in formulations with higher MG levels. In formulations containing higher levels of MG, the drug release is slightly reduced. Conclusion: The study summarized that amoxicillin trihydrate is capable of good stomach-specific drug delivery by carbomer 934P and enhanced by mastic gum when prepared as mucoadhesive microspheres that are cost-effective, operational, and stable. This approach also resolves the gastric retention of ATH to eradicate H. pylori and the mastic gum has proved an anti-ulcer possession.

Impact of Azadirachta indica Fruit Mucilage on particle size and swelling index in Central Composite Designed Acyclovir mucoadhesive microspheres

The drive of this exploration is to investigate the mucoadhesive assets of A. indica (Azadirachta indica) fruit mucilage by incorporating it into mucoadhesive microspheres with Acyclovir (AVR) as a model drug. The study was performed to check the impact of the mucilage proportion on particle size and swelling index. Nine batches of AVR mucoadhesive microspheres were made with varying proportions of Polyacrylic acid 934P and A. indica fruit mucilage (AIFM). A central composite design with design expert software to check the impact of dependent variables (A. indica mucilage and Polyacrylic acid 934 P levels) on particle size and swelling index as a response. As part of congeniality studies, the batches were examined for their physical constraints, AVR contents, and liberation. The particle size was found to be 35.2±0.3-48.1±0.6μm. In batch B-1, the particle was least sized compared to the larger size in B-5. The investigation found that the particle size and the swelling index depended on AIFM and Polyacrylic acid proportions. The research discovered that AVR was systematically released in a controlled manner and that the entrapment efficacy, mucoadhesion, drug content, and other constraints were found to be good. Acyclovir is capable of good stomach-specific drug delivery by Polyacrylic acid 934P and enhanced by A. indica fruit mucilage when prepared as mucoadhesive microspheres. Scanning electron microscopy reveals that the microspheres were spherical with a fairly smooth surface.

Neem Fruit Mucilage-Aided Mucoadhesive Microspheres of Acyclovir Using 32 Factorial Design With Design-Expert Software

The study aims to investigate the mucoadhesive properties of neem fruit mucilage by incorporating it into mucoadhesive microspheres with Acyclovir (ACR) as a model drug. Nine interpretations of mucoadhesive microspheres were made with carbomer-934P and varying proportions of neem fruit mucilage (NFM). A central composite design with Design Expert software to check the impact of independent variables (neem mucilage and carbomer 934P levels) on entrapment efficacy and mucoadhesion time. As part of congeniality studies, the microspheres were examined for ACR content and liberation. The study revealed that ACR entrapment increased with increase in NFM levels in the formulations and that the mucoadhesion time was greater in formulations with higher NFM levels. In the formulations containing higher levels of NFM, the drug release was slightly reduced. Acyclovir is capable of good stomach-specific drug delivery by carbomer 934P and its delivery is enhanced by neem fruit mucilage when prepared as mucoadhesive microspheres.

Natural Polysaccharides: An Overview of their Role in the Development of Microparticles for Stomach Targeting

Development of safe and efficacious gastro-retentive dosage forms for stomach specific drug delivery have profound importance in pharmaceutical industry. Different approaches used for gastro retention are discussed with a special focus on the floating drug delivery systems. Natural polymers have great demand in drug delivery as they encompass polymers with many functional groups, wide range of molecular weights, varying chemical composition, for the most part, low toxicity and biodegradability yet high stability. Most of these polymers have been approved by many regulatory bodies all over the globe for their usage as pharmaceutical excipients; hence, their adoptability in formulation and development is hassle free. Natural polysaccharides have been investigated for drug delivery as well as biomedical applications. This review provides an overview of different stomach specific natural polymers used or currently being used specially for controlled drug delivery and the advantages of microparticles for stomach specific drug delivery including their preparation methodologies etc. The review also emphasizes a brief summary of existing challenges associated with microparticles as delivery system for targeting drugs in the stomach and alternative methods/solutions adopted to overcome the same down the years.

32 FACTORIAL DESIGN SCREENED ABELMOSCHUS ESCULENTUS FRUIT MUCILAGE ABETTED FLOATING MICROSPHERES OF CLARITHROMYCIN FOR EXTERMINATING H. PYLORI

The study aims to investigate the floating possessions of Abelmoschus esculentus fruit mucilage by incorporating it into floating microspheres with Clarithromycin. Nine interpretations of floating microspheres were made with Sodium alginate (SA) and varying proportions of Abelmoschus esculentus fruit mucilage (AEFM). A central composite design with design expert software to check the impact of independent variables (AEFM and SA levels) on entrapment efficacy and floating time (FT). As part of congeniality studies, the microspheres were scrutinized for Clarithromycin (CMN) content and its release. The research discovered that CMN entrapment increased with an increase in AEFM levels in the formulations and that the floating time (FT) was greater in formulations with higher AEFM levels. In formulations containing higher levels of AEFM, the drug release is slightly reduced. The study revealed that Clarithromycin is capable of good stomach-specific drug delivery by formulating it with SA as floating microspheres and the assets were enhanced by AEFM.

Evaluation of in situ gel forming system loaded with etoricoxib and herbal adjuvant nanoparticles against human colon cancer cell lines (HT-29)

The aim of the research work was to fabricate the nanosuspension of etoricoxib with polyherbal components (extract of ginger root and basil leaf) to enhance the solubility of API; furthermorein situ gel forming system for stomach specific drug delivery was prepared utilizing formulated nanosuspension as base. The objective of the present research is to enhance the solubility of poorly aqueous soluble drug by fabricating nanoparticles and improve their residence time within stomach by formulating in situ gel forming system. Tamarind seed polysaccharide as polymer, etoricoxib as drug, ethanolic extract of ginger (GE) and basil (BE), was used for preparation of nanoparticles.Solvent antisolvent precipitation method was used to prepare nanoparticles. The fabricated nanoparticles were evaluated for various parameters such as physical appearance, Scanning electron microscope, drug content, in-vitro drug release. For preparation of in-situ gel containing nanoparticles, tamarind seed polysaccharides, calcium carbonate and sodium alginate were used. The prepared formulations were evaluated for different characterization parameters such as,- pH, viscosity, floating behaviour, drug content, in-vitro drug release and in-vitro cytotoxic study. The in-situ gel containing nanoparticles were successfully prepared and evaluated. Firstly, the nanoparticles were evaluated for physical appearance, Scanning electron microscope, drug content, in-vitro drug release and found that the formulations were clear as well as homogenous, size of nanoparticles was evaluated in the range of 498nm to 587nm, the drug content of etoricoxib was found in the range of 71.38±0.01 (F5) to 79.45±0.01 (F6), the drug content of GE was found in the range of 69.25±0.05 (F4) to 74.25±0.02 (F1) and the drug content of BE was 69.48±0.09 (F1) to 75.59±0.08 (F6). The drug release was taken up to 12 h and found to be 99%. In-situ gel containing nanoparticles were also evaluated for different parameters such as pH, viscosity, floating behaviour, drug content, and in-vitro drug release. The pH of the prepared formulation was found to be in the range of 7.1±0.04 to 7.5±0.02. The viscosity of the prepared formulation was found in the range of 11.25±0.023 to 12.78 ±0.025. The lag time was found in the range of 11 to 20 sec and floating time was upto 24 h. The drug release was taken up to 8 h and found to be 99±0.2%. It can be concluded that etoricoxib with phytoconstituents (GE and BE) improved its potential to control the growth of human colon cancer cell line (HT-29) in in-vitro conditions. It was concluded from the findings that the in-situ gel containing nanoparticles of etoricoxib from solvent antisolvent method was successfully prepared and found that it has improved the solubility of the poorly soluble drug etoricoxib and dissolution rates.

Formulation of Gastro-retentive Floating Tablets of Valsartan by 2 power 2 Factorial Designs: In vitro and In vivo Evaluations

An oral dosage form containing gastro-retentive floating tablets forms a stomach-specific drug delivery system for the treatment of hypertension. Valsartan belongs to the BCS class II (poo Classification System). It is desirable to improve the extent of bioavailability (23%). The objective of the present study was to apply design of experiment to optimize floating drug delivery of valsartan by employing 22 factorial design. Improvement of the aqueous solubility of valsartan was done by solid dispersions using hot melt extrusion technique. Plasdone S630 copovidone is a variable carrier and drug to carrier ratio of 1:2 was optimized. Valsartan floating tablets were prepared by employing factorial design (22), where HPMC K15M (X1) and pregelatinized starch (X2) were independent variables and drug dissolution was the dependent parameter (Y1) to prepare matrix tablets. The factorial analysis, steepest ascent method was utilized for obtaining optimized formulation. In vitro evaluation, In vivo radiographic study and biopharmaceutical analysis in rabbits for valsartan optimized formulation (FT-5). Floating lag time (FLT) for valsartan optimized formulation (FT-5) was 15 s and total floating time (TFT) of the tablets was about 33 h, which was satisfactory. A four-point (1 h, 4 h, 8 h and 16 h) dissolution analysis gave satisfactory dissolution profile up to 24 h. The release kinetics of valsartan optimized formulation (FT-5) followed zero order and the release mechanism was found to be Korsemeyer Peppas model, i.e. swelling type. The dissolution efficiency for valsartan floating tablets was 1190.89% against the marketed formulation of 39.77%. The accelerated stability profile of valsartan optimized formulation (FT-5) was evaluated in terms of drug content and percent cumulative dissolution of valsartan in 24 h, in a 6 months study. In vivo X-ray image study for valsartan optimized formulation (FT-5) indicated the presence of intact tablet up to 12 h in gastric region of rabbit. The biopharmaceutical analysis in rabbits was conducted for valsartan optimized formulation (FT-5). The HPLC method was established and validated for the in vivo analysis. The Cmax was 453.2 ng/mL compared to that of the marketed tablets (522.4 ng/mL). The mean residence time (MRT) for the valsartan optimized formulation (FT-5) was 14.82 h as against 4 h for marketed tablet. The relative bioavailability of valsartan optimized formulation (FT-5) was 650% higher than the marketed tablet. To overcome the poor bioavailability of valsartan, it was suitably modified using hot-melt extrusion for improving therapeutic outcome. In conclusion, gastro-retentive drug delivery system is an excellent approach for improving the bioavailability of valsartan. 

Formulation and investigation of crushed puffed rice-chitosan-HPMC based polymeric blends as carrier for sustained stomach specific drug delivery of piroxicam using 3(2) Taguchi mathematical design studies

In the present experimental investigation an attempt has been made to assess the utility of Crushed Puffed Rice (CPR)-High Molecular Weight Chitosan (HMWCH)-Hydroxypropyl Methylcellulose K15M (HPMC K15M) as a polymeric carrier for the sustained stomach delivery of Piroxicam (PRX). A total of nine formulations were prepared by using 3 (2) Taguchi factorial design, physically blending drug and polymer(s) followed by encapsulation into hard gelatin capsules size 1. The prepared capsules were evaluated for various performance such as weight variation, drug contents, in vitro buoyancy and drug release in 0.1 M HCl. The effect of drug loading on in vitro performance of the formulations was also determined. Crushed puffed rice (CPR) remained buoyant for up to average time span of 06 hr as an unwetted irregular mass in 0.1 M HCl. However, when combined with HMWCH or HPMC K15M or HPMC K15M + HMWCH a low -density cylindrical raft type hydrogel was formed which remained buoyant for up to 12 hr and released up to 99% drug in a sustained manner from 8 to 12 hr following zero order release kinetics. It was also observed that drug release from drug + CPR matrices followed Fickian mechanism. Combination of CPR + HMWCH or HMWCH + HPMC K15M also follows Fickian mechanism. Obtained data from the research work suggests that CPR in combination with HMWCH or HPMC K15M or HPMC has sufficient potential to be used as a carrier for stomach specific delivery of gastric irritant drug like PRX.Soni et al., International Current Pharmaceutical Journal, April 2018, 6(11): 61-80http://www.icpjonline.com/documents/Vol6Issue11/01.pdf

FORMULATION DEVELOPMENT AND EVALUATION OF NOVEL DUAL-COMPARTMENT CAPSULE FOR STOMACH SPECIFIC DRUG DELIVERY

The aim of the proposed research work was to develop a unique dual-compartment capsule dosage form of ciprofloxacin hydrochloride (CHL) which is well-known to have short elimination half-life and narrow absorption window. Formulated dual-compartment capsules were evaluated for its suitability for stomach specific drug delivery by employing different polymers such as Guar gum, Xanthan gum. Formulations were assessed for interaction studies, in vitro buoyancy, effect of polymer concentration on drug release and release kinetics. Experimental results demonstrated that natural polymers can be effectively exercised to formulate capsule dosage form for improved gastro retention and sustained drug release; which may be better and economic alternative for synthetic polymers.

Preparation and characterization of spray-dried valsartan-loaded Eudragit® E PO solid dispersion microparticles

The purpose of this study was to develop the immediate release stomach-specific spray-dried formulation of valsartan (VAL) using Eudragit® E PO (EPO) as the carrier for enhancing dissolution rate in a gastric environment. Enhanced solubility and dissolution in gastric pH was achieved by formulating the solid dispersion using a spray drying technique. Different combinations of drug–polymer–surfactant were dissolved in 10% ethanol solution and spray-dried in order to obtain solid dispersion microparticles. Use of the VAL–EPO solid dispersion microparticles resulted in significant improvement of the dissolution rate of the drug at pH 1.2 and pH 4.0, compared to the free drug powder and the commercial product. A hard gelatin capsule was filled with the VAL–EPO solid dispersion powder prior to the dissolution test. The increased dissolution of VAL from solid dispersion microparticles in gastric pH was attributed to the effect of EPO and most importantly the transformation of crystalline drugs to amorphous solid dispersion powder, which was clearly shown by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (P-XRD) studies. Thus, VAL, a potential antihypertensive drug in the form of a solid dispersion microparticulate powder, can be effectively delivered in the immediate release dosage form for stomach-specific drug delivery.

Raft forming Buoyant Ph Dependent Thixotropic Gelling Systems Incorporated with Gelucire 43/01 as a Potential Stomach Specific Drug Delivery System for Famotidine

Famotidine (FMT) is known as a histamine blocker (H2) that inhibits stomach acid production and it is commonly used in the treatment of peptic ulcer disease and gastric-esophageal reflux disease. It has a short half life (2.5-3.5 hours), low bioavailability (40-45%). It has excellent solubility in acidic pH just reverse in alkaline pH. Therefore an attempt has been made to develop raft buoyant gastro-retentive sustains release delivery system with in situ gelling property which is based on thixotropy behavior. Twelve formulations (Excluding two controlled formulations i.e. F and F*) were designed to contain 40 mg of FMT using Chitosan; CH (cationic polymer), Sodium Alginate; SA (anionic polymer), Gelucire 43/01; G 43/01 (lipid phase) as retardant and adhesive polymers. Emulgel was prepared and evaluated for their physicochemical properties like buoyancy and lag time, cumulative % drug release, drug release kinetics and drug excipient interaction studies by thermal studies and functional group characterization. All formulations showed that with the increase in concentration of the polymer, the gel strength increased, but the % drug release decreased F8>F12>F11>F6>F5>F10>F7>F9>F3>F4>F1>F2>F*>F. Formulations F9, F10, and F12 were found to be optimum. They followed the non-ficikian mechanism of drug release.

Evaluation of Chitosan Based Polymeric Matrices for Sustained Stomach Specific Delivery of Propranolol Hydrochloride

The objective of the present investigation was to explore the potential of Chitosan based polymeric matrices as carrier for sustained stomach specific delivery of model drug Propranolol Hydrochloride. Briefly, single unit hydrodynamically balanced (HBS) capsule formulations were prepared by encapsulating in hard gelatin capsules, intimately mixed physical mixtures of drug, and cationic low molecular weight Chitosan (LMCH) in combination with either anionic medium viscosity sodium alginate (MSA) or sodium carboxymethylcellulose (CMCNa). The effect of incorporation of nonionic polymers, namely, tamarind seed gum (TSG) and microcrystalline cellulose (MCCP), was also investigated. It was observed that HBS formulations remained buoyant for up to 6 h in 0.1 M HCl, when LMCH : anionic/nonionic polymer ratio was at least 4 : 1. It was also observed that LMCH has formed polyelectrolyte complex (PEC) with MSA (4 : 1.5 ratio) and CMCNa (4 : 1 ratio) in situ during the gelation of HBS formulations in 0.1 M HCl. The retardation in drug release was attributed to the PEC formation between LMCH and MSA/CMCNa. Incorporation of MCCP (rapid gel formation) and TSG (Plug formation) was found to be innovative. From the data, it is suggested that Chitosan based polymeric matrices may constitute an excellent carrier for stomach specific drug delivery.

Buoyancy-generating agents for stomach-specific drug delivery: an overview with special emphasis on floating behavior.

Gastric retentive drug delivery provides a promising technology exhibiting an extended gastric residence and a drug release independent of patient related variables. It is usually useful in improving local gastric treatment as well as overcoming drug-related problems .i.e. drugs having narrow absorption window, short half-life or low intestinal solubility. Buoyancy is considered one of the most promising approaches for gastro-retention of dosage forms. Floating drug delivery systems have a bulk density lower than gastric fluids and thus remain buoyant in the stomach causing an increase in gastric residence time. The buoyancy of these systems is attained by the aid of substances responsible to generate the low density. Various agents with different mechanisms were adopted either gas-generating agents, air entrapping swellable polymers, inherent low density substances, porous excipients, hollow/porous particles inducing preparation techniques or sublimating agents. Therefore, this review gives an exclusive descriptive classification of the different categories of these buoyancy-generating agents while representing the related research works. An overview is also conducted to describe relevant techniques assessing the floating behavior of such dosage forms either in vitro or in vivo. Finally, a collection representing FDA-approved floating pharmaceutical products is adopted with emphasis on the buoyancy-generating agent type used in each product.

Floating-bioadhesive gastroretentive Caesalpinia pulcherrima-based beads of amoxicillin trihydrate for Helicobacter pylori eradication

Context: An oral dosage form containing floating bioadhesive gastroretentive microspheres forms a stomach-specific drug delivery system for the treatment of Helicobacter pylori.Objectives: To prepare and evaluate controlled release floating bioadhesive gastroretentive chitosan-coated amoxicillin trihydrate-loaded Caesalpinia pulcherrima galactomannan (CPG)-alginate beads (CCA-CPG-A), for H. pylori eradication.Materials and methods: CCA-CPG-A beads were prepared by ionotropic gelation, using 23 factorial design with quantity of drug, combination of CPG with sodium alginate and concentration of calcium chloride as variables. Beads facilitated mucoadhesion to gastric mucosa with floating nature caused by chitosan coating for wide distribution throughout GIT. Developed beads were evaluated for characteristics like beads size-morphology, entrapment efficiency, DSC, XRD, FTIR, swelling ratio, in vitro mucoadhesion, in vitro drug release, in vitro floating and in vitro H. pylori growth inhibition studies. CCA-CPG-A beads were studied in Wistar rats for in vivo gastric mucoadhesion, in vivo H. pylori growth inhibition studies using PCR amplification of isolated DNA, rapid urease test.Result: Developed beads possess drug release of 79–92%, entrapment efficiency of 65–89%, mucoadhesion of 61–89%. In vivo mucoadhesion study showed more than 85% mucoadhesion of beads even after 7th hour. In vitro–in vivo growth inhibition study showed complete eradication of H. pylori.Discussion: CPG-alginate and chitosan in beads interacts with gastric mucosubstrate surface for prolonged gastric residence with floating bioadhesion mechanism for H. pylori eradication in rats.Conclusion: Floating bioadhesive CCA-CPG-A beads offer a promising drug delivery system for H. pylori eradication at lower dose, reduced adverse effect and enhance bioavailability.

Design and Evaluation of Imatinib Mesylate Loaded Microspheres for Stomach Specific Drug Delivery

Aims: The aim of the present work was to design and evaluate the Imatinib mesylate microspheres using natural and semi synthetic polymers for stomach specific drug delivery. Study Design: Design and Evaluation of Imatinib Mesylate loaded microspheres Place and Duration of the Study: The study was carried out in Department of Pharmaceutics, JKKMMRF’s Annai JKK Sampoorani Ammal College of Pharmacy, between November 2012 and July 2013. Methodology: The microspheres were prepared using Sodium alginate as a polymer by Emulsification Ionic Gelation Technique. Copolymers of natural origin namely Guar gum, Karaya gum, Chitosan and semi synthetic origin namely Hydroxy propoylmethyl cellulose K4M, K15M, K100M are used as mucoadhesive polymers. The prepared microspheres were evaluated for their percentage yield, entrapment efficiency, degree of swelling, particle size, surface morphology and in-vitro mucoadhesion, drug release studies. Drug release kinetics was determined from drug release data. Selected formulations are subjected to stability studies under varying conditions of temperature and humidity. Results: The production yields of microspheres were found to be between 76.74 to 88.18%. Percentage drug entrapment efficiency of Imatinib mesylate microspheres was ranged from 65.51 to 88.78%. Particle size of the prepared microspheres was in the size range of 440-810µm. SEM analysis revealed that all the prepared microspheres were discrete, spherical in shape. The in-vitro mucoadhesive study demonstrated that Hydroxy propoylmethyl cellulose adhered to the mucus to a greater extent than other polymers. The in-vitro release study shows that, retarded release with increase in percentage of polymers. The release of drug from the microspheres followed Krosmeyer Peppas kinetics. After the stability studies, the formulations remained stable at the end of storage period. Conclusion: Based on the results, it was concluded that, the formulations with natural polymers were found to be best than semi synthetic polymers for the oral delivery of Imatinib mesylate.

Formulation and Evaluation of Bilayered Gastroretentable Mucoadhesive Patch for Stomach-Specific Drug Delivery

The aim of the present work was to develop and evaluate stomach-specific controlled release, gastroretentable mucoadhesive patch of lercanidipine HCl. This drug is essentially soluble in gastric pH range of 1- 4 and have a partition coefficient (log p-value) of 6.1; according to this concept, it has been decided to formulate the gastroretentive bioadhesive patch. The patch system consisted of a drug release rate controlling film, using the combination of Eudragit RSPO and RLPO; mucoadhesive film by using the combination of various hydrophilic polymers. Bilayered patch were made by using the selected batch of two films using the layering method and evaluated for the various parameters like in vitro swelling study, ex vivo mucoadhesive strength. Film was folded into a hard gelatin capsule, evaluated for in vitro drug release in pH 1.2 containing 0.2% (w/v) sodium lauryl sulphate (SLS), and in vivo bioavailability in rabbits. Patches could control the drug release up to 12 h, having mucoadhesion strength in the range of 4.05±0.4 N to 4.52±0.12 N. In vivo bioavailability results indicate that the gastroretentive patch system provides a novel way to retain the drug matrix for the longer period of time in a stomach, enhance drug absorption and thereby offer a promising strategy for gastroretentive mucoadhesive drug delivery for the lercanidipine HCl.

Low molecular mass chitosan as carrier for a hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride

Chitosan has become a focus of major interest in recent years due to its excellent biocompatibility, biodegradability and non-toxicity. Although this material has already been extensively investigated in the design of different types of drug delivery systems, it is still little explored for stomach specific drug delivery systems. The objective of the present investigation was to explore the potential of low molecular mass chitosan (LMCH) as carrier for a hydrodynamically balanced system (HBS) for sustained delivery of water soluble drug ciprofloxacin hydrochloride (CP). Various formulations were prepared by physical blending of drug and polymer(s) in varying ratios followed by encapsulation into hard gelatin capsules. All the formulations remained buoyant in 0.1 mol L⁻¹ HCl (pH 1.2) throughout the experiment. Effect of addition of xanthan gum (XG) or ethyl cellulose (EC) on drug release was also investigated. Zero order drug release was obtained from the formulations containing LMCH alone or in combination with XG, and in one instance also with EC. Our results suggest that LMCH alone or in combination with XG is an excellent material for stomach specific sustained delivery of CP from hydrodynamically balanced single unit capsules.

Formulation and in vivo evaluation of Floating Microspheres of Misoprostal

Prostaglandin (PG) has been reported to be an important protective and acid‐suppressive factor in the gastric mucosa. The objective of the study was to develop and evaluate a stomach specific drug delivery system for controlled release of Misoprostal a PE analogue for gastric ulcer induced NSAIDs. Floating microspheres were prepared by emulsification‐solvent evaporation method using ethylcellulose as a polymer, carbopol as mucoadhesive polymer. Ulcers were induced by the oral administration of absolute ethanol (5 ml/kg) to 24 h fasted Wistar male rats (n =8), weighing 200 g. Sodium bicarbonate solution, misoprostal solution and drug‐loaded microspheres were tested. Formulations were administered orally 1 h before the administration of ethanol. Prior to the oral administration, rats were anesthetized with ethylic ether. After 2 h of ethanol administration, animals were sacrificed; the stomachs were removed, opened along the greater curvature and examined for lesion measurements. Ulcer indexes (UI) were calculated. The in vivo evaluation showed that ulcer index values were 0.61 ± 0.14 for the sodium bicarbonate solution, 0.58 ±0.18 for the misoprostal and 0.11 ± .06 for the misoprostal‐loaded microspheres. The Kruskal‐Wallis test detected statistical differences (p =0.002) between the ulcer indexes. The multiple analyses (Student‐Newman‐Keuls) showed that the misoprostal loaded micro particles presented a gastric ulcer index statistically lower than the sodium bicarbonate solution (p = 0.001) and the misoprostal solution (p = 0.021). The percentages of ulceration inhibition were 31 and 75% after the administration of misoprostal solution and microspheres, respectively. In conclusion, the in vivo evaluation showed that the microspheres presented ulcer index lower than the solutions, showing that misoprostal‐loaded microparticles were efficient in protecting the stomach against ulcer formation.

IN VIVO EVALUATION OF MISOPROSTOL FLOATING MICROSPHERES

Prostaglandin (PG) has been reported to be an important protective and acid suppressive factor in the gastric mucosa. The objective of the study was to develop and evaluate a stomach specific drug delivery system for controlled release of Misoprostal a PE analogue for gastric ulcer induced NSAIDs. Floating microspheres were prepared by emulsification-solvent evaporation method using ethyl cellulose as a polymer, carbopol as mucoadhesive polymer. Ulcers were induced by the oral administration of absolute ethanol (5 mL/kg) to 24 h fasted Wistar male rats (n=8), weighing 200 g. Sodium bicarbonate solution, misoprostal solution and drug loaded microspheres were tested. Formulations were administered orally lh before the administration of ethanol. Prior to the oral administration, rats were anesthetized with ethylic ether. After 2 h of ethanol administration, animals were sacrificed; the stomachs were removed, opened along he greater curvature and examined for lesion measurements. Ulcer indexes (UI) were calculated. The in vivo evaluation showed that ulcer index values were 0.61 ± 0.14 for the sodium bicarbonate solution, 0.58 ±0.18 for the misoprostal and 0.11 ± 0.06 for the misoprostal-loaded microspheres. The Kruskal¬Wallis test detected statistical differences (p =0.002) between the ulcer indexes. The multiple analyses (Student-Newman-Keuls) showed that the misoprostal loaded microspheres presented a gastric ulcer index statistically lower than that of the sodium bicarbonate solution (p = 0.001) and the misoprostal solution (p = 0.021). The percentages of ulceration inhibition were 31 and 75% after the administration of misoprostal solution and microspheres, respectively. In conclusion, the in vivo evaluation showed that the microspheres presented ulcer index lower than the solutions, showing that misoprostal-loaded microspheres were efficient in protecting the stomach against ulcer formation. Key words: Misoprostal, microspheres, ulcer index,