Prolonged Gastric Residence Time Research Articles

Patient-Centric Approaches to Gastroretentive Floating Tablets: Tailoring for Diverse Clinical Needs

Gastroretentive tablets have emerged as a promising platform for controlled drug delivery, offering the potential for prolonged gastric residence time and enhanced therapeutic outcomes. This comprehensive review explores the paradigm shift towards patient-centric approaches in the development of gastroretentive tablets. The journey begins with an examination of the historical evolution of gastroretentive technologies, tracing advancements in formulation techniques, materials, and technologies that have paved the way for patient-centric designs. The review delves into patient-centric formulation strategies tailored for diverse populations, including pediatrics and geriatrics. It highlights the importance of considering patient-specific needs, preferences, and physiological characteristics in optimizing dosage forms. Regulatory considerations and compliance-enhancing features are scrutinized, providing insights into the delicate balance between personalized medicine and regulatory expectations. Real-world applications are illuminated through case studies, offering success stories across pediatric, geriatric, and personalized medicine contexts. Clinical outcomes, including adherence metrics and patient satisfaction, provide tangible evidence of the impact of patient-centric gastroretentive tablets. Challenges in formulation development and regulatory implementation are critically examined, with a focus on technical hurdles and strategies for navigating evolving regulatory landscapes. The conclusion distills key findings and outlines implications for future research and clinical practice, emphasizing continued innovation, strategic regulatory engagement, and interdisciplinary collaboration. This review serves as a comprehensive resource for researchers, clinicians, and regulatory professionals engaged in advancing patient-centric gastroretentive tablets. It offers a roadmap for the integration of innovative technologies into clinical practice, fostering a patient-centered approach in the evolution of controlled drug delivery systems.

EPLERENONE FLOATING MICROSPHERES: RADIOGRAPHIC AND PHARMACOKINETIC STUDIES IN RABBITS

Objective: The objective of the present investigation was to evaluate gastro-retentive performance and pharmacokinetic parameters of Eplerenone-optimized floating microspheres compared with formulated floating tablets. Methods: Microsphere contains antihypertensive drug Eplerenone as a core material encapsulated with the polymeric membrane for sustained drug release were prepared by solvent diffusion-evaporation technique. The prepared microspheres were evaluated for qualitative and quantitative parameters. The optimized formulation showed favorable in vitro floating and drug release profile. The gamma scintigraphy of the formulation was carried out in rabbit in order to determine the floating ability of the final formulation with barium sulfate. Prolonged gastric residence time of over 12 h was achieved in all the animals. Eplerenone-loaded optimized formulation was orally administered to rabbit and blood samples were used to determine pharmacokinetic parameter by using WinNonlin software 3.0 version. Results: Eplerenone floating microsphere, which are compared with pharmacokinetic parameters of the Floating tablet showed improved parameters of Cmax; similarly, time to reach peak plasma concentration (t-max) for Eplerenone Floating microspheres was 4 times increased against Floating tablet formulation. The area under the curve (AUC) for formulated floating tablet was found to be 9.69 µg/ml, whereas for floating microspheres it was 16.28 µg/ml, for formulated floated tablet absorption rate constant Ka was 1.61 h, elimination rate constant was 0.112 h and elimination half-life 6.2 h. The comparison of these data undoubtedly shows that the Cmax was not much valid, but AUC was increased to about 1.68 times in case of floating microspheres, absorption rate constant was found to be decrease 3.22 times when related to the floating microspheres, whereas Ke was found to be decrease 2.11 times when equated to floating microspheres, elimination half-life was increased by almost about two times. Conclusion: Eplerenone floating microsphere, which are compared with pharmacokinetic parameters of the floating tablets showed enhanced parameters of the formulated due to floating nature of the present designed formulation.

Formulation and evaluation of floating controlled drug delivery of anti-ulcer drug loaded microballoons

An attempt has been made to develop floating drug delivery system for improving the drug bioavailability by prolongation of gastric residence time of Famotidine in the stomach. The floating microballoons were prepared using polymer Eudragit RS100, HPMC K100M and Ethyl Cellulose. Famotidine was used as the model drug. Nine formulations (F1 to F9) were prepared by varying the ratio of polymers. The prepared Famotidine loaded micro balloons were characterized for percentage yield, particle size analysis, surface morphology, micromeritic properties, drug entrapment efficiency, buoyancy studies and in-vitro drug release. The formulated micro balloons were free flowing. The micro balloons with Eudragit RS100 showed higher buoyancy when compared with HPMC K100M and Ethyl Cellulose. On the basis of micromeritic properties, particle size, percentage yield, morphology, buoyancy study, drug entrapment, optimum in-vitro drug release and satisfactory release kinetics, formulation F2 was selected as an optimum formulation

Advances in the Preparation Techniques of Floating Microspheres with Exploration of AI Tool in Product Development

This review paper focuses on recent developments in gastroretentive drug delivery systems for controlled release oral drug administration. Gastric emptying’s variability presents challenges to drug delivery systems, making gastroretentive drug delivery systems increasingly popular for retaining drugs in the stomach and ensuring gradual release. Traditional oral delivery systems often fail to overcome gastrointestinal obstacles, resulting in incomplete drug release, decreased efficacy. Thus, achieving prolonged gastric residence times is crucial, particularly for drugs with upper small intestine absorption windows. Gastro retentive drug delivery system provide for prolonged drug release in the upper digestive system, improving bioavailability for drugs with narrow therapeutic windows, extending dosing intervals, and enhancing patient compliance. The purpose of this review is to discuss recent advancements in the preparation techniques for floating drug delivery systems and highlights the incorporation of AI-Enabled design and optimization in drug release behavior. These technologies enhance precision and efficiency in gastroretentive drug delivery systems development, promising further improvements in drug delivery effectiveness and patient adherence.

80-LB: Evaluation of the Pharmacokinetics of Glucagon-Like-Peptide-1 (GLP-1) Receptor Agonist Delivered through the BIOJET Oral Biotherapeutic Delivery Platform in Porcine Model

Glucagon-like-peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and suppress glucagon release. Semaglutide is a GLP-1 agonist currently injected subcutaneously or taken orally to treat type 2 diabetes and for weight management. However, oral administration of protein/peptide therapeutics has proven difficult due to the harsh conditions of the upper gastrointestinal tract (GIT) and poor absorption rates in the small intestine. The BIOJET™ oral biotherapeutic delivery platform is an ingestible drug-device combination developed to increase drug bioavailability via needleless jet injection in the proximal small intestine following oral administration. Previous testing of an earlier, autonomously triggered version of the device in animal models was presented at ACG 2022. In this study we evaluated the pharmacokinetics (PK) of semaglutide delivered through the BIOJET device in a porcine model. Due to prolonged and variable gastric residence times in the porcine model, devices filled with semaglutide (~1mg) were administered by intraduodenal (ID) endoscopic placement and activated in the proximal small intestine of Yucatan swine. PK blood sampling was performed from 0 to 240 hours post-dose to evaluate systemic exposure of semaglutide. Seven of eight (7/8) devices were successfully placed and activated in the duodenum. All seven animals showed detectable drug levels up to ten days post-dosing and had an oral bioavailability average of 37% ± 15% (CV: 40%), ranging from 19%-60% compared to IV control. No significant clinical signs were observed in the animals. This study demonstrated that administration of the BIOJET device has the potential to achieve a magnitude greater bioavailability than the currently marketed oral semaglutide (< 1%). The BIOJET device could provide an alternative for the oral administration of large molecules and may improve patient compliance. Disclosure S. N. Lee: Employee; Biora Therapeutics. C. A. Stork: Employee; Biora Therapeutics. R. O. Valenzuela-rivas: Employee; Biora Therapeutics. M. Walker: Employee; Biora Therapeutics. B. J. Smith: Employee; Biora Therapeutics. J. A. Smith: None. N. Quintana: None. C. Wahl: Employee; Biora Therapeutics. S. Singh: None.

A Review on Gastroretentive Drug Delivery System

The purpose of writing this review was to investigate, compile and present the recent as well as past literatures in more concise way with special focus on approaches which are currently utilized in the prolongation of gastric residence time. One novel approach in this area is Gastro Retentive Drug Delivery System (GRDDSs). GRDDSs can improve the controlled delivery of drugs that have an absorption window by continuously releasing the drug for a prolonged period of time before it reaches its absorption site. These includes floating system, swelling and expanding system, bio/mucoadhesive system, high density system and other delayed gastric emptying devices. The present review addresses briefly about the, factors controlling gastric retention, advantages, Disadvantages and applications of gastroretentive drug delivery systems, Commonly used drug in formulation of GRDDS,Gastroretentive products available in the market, types of GRDDS.

S1566 Evaluation of the Pharmacokinetics of PGN-OB1 Following Oral Administration of an Oral Biotherapeutics Delivery System (OBDS) in Yucatan Swine

Introduction: Biologics/peptides/nucleic acids are highly effective drugs; however, oral delivery of these therapeutics has proved to be difficult due to the harsh conditions of the upper gastrointestinal tract (GIT) and the poor absorption rate in the small intestinal mucosa. We aimed to develop an oral biotherapeutic delivery system (OBDS) that protects these biomolecules from degradation in the upper GIT and increases oral bioavailability via needless injection in the submucosal space of the small intestine. We describe the development of models to assess the functional capability of the OBDS capsule. A Yucatan minipig model was chosen to better represent the pharmacokinetic properties of submucosal injection in humans and evaluate the injection efficiency of OBDS in vivo. Methods: Due to prolonged and variable gastric residence times in the swine model, the semi-autonomous OBDS capsules containing a variant of adalimumab (PGN-001), PGN-OB1, were administrated by intraduodenal endoscopic placement (ID) and released into the proximal small intestines of the female Yucatan swine. Blood samples post-ID dosing were collected to evaluate the injection efficiency of the OBDS compared with the IV control group. Results: All OBDS capsules were successfully advanced through the pyloric sphincter via endoscopic placement, without early deployment, and released in the proximal duodenum to naturally transit and deploy in vivo. Out of 13 animals dosed, 8 animals showed detectable drug levels (Figure), and an oral bioavailability average of 22% or 25% (range from 7-55%) excluding an animal showing a late deployment at 72hr post-dose. The variability in the swine model is believed to be due to physiologic variability that may not directly translate to humans including variability in small intestinal transit time, and more frequent and larger, gas and fluid pockets in the swine. Conclusion: Here we have provided proof-of-concept of a semi-autonomous OBDS device that can achieve as high as 55% bioavailability of a variant of adalimumab that is a magnitude higher than current oral protein or peptide delivery technology in the market and at levels much closer to the subcutaneous route of administration estimated in human trials. The OBDS capsules could potentially provide a better alternative for the non-invasive route of administration with better patient compliance.Figure 1.: Plasma concentration of PGN-001 treated with ID and IV over time

Application of Quality by Design Approach in Development of Cefixime Trihydrate Loaded Gastro-retent

Cefixime is an antibiotic that belongs to the 3rd generation cephalosporin antibacterial and acts by interrupting the cell wall synthesis of bacteria. It is a weakly acidic drug primarily absorbed through the stomach and upper intestine as a unionized drug. The drug is incompletely absorbed from GIT, leading to poor bioavailability. The current research focuses on developing gastro-retentive mucoadhesive microspheres loaded with cefixime trihydrate. The drug remains in the unionized form in acidic pH, showing enhanced absorption through the stomach. Mucoadhesive microspheres of cefixime trihydrate were prepared using HPMC K15M and Carbopol 971P as carrier polymer and mucoadhesive polymer, respectively. The formulation was prepared by using the spray drying technique. Further, the in-vitro evaluation of the mucoadhesive property of cefixime microspheres was done on the goat stomach mucosa. The study showed a strong mucoadhesion of 82% for an extended period of gastroprotection up to 6 hours. The in-vitro drug release study of microspheres was performed using 0.1 N HCl. The prepared formulation exhibited extended release for up to 8 hours. It is concluded from the above studies that the current formulation has been elicited prolonged gastric residence time as well as extended-release and provided an opportunity for better and enhanced absorption of the drug. Thus, the formulation may be projected for better therapeutic value, probably by improving the bioavailability of the experimental drugs.

Different evaluation parameters of floating microsphere of ofloxacin

The Floating Microsphere of Ofloxacin requires a novel gastroretentive drug delivery system which can provide an extended period of time in stomach and improve oral bioavailability. Floating microspheres were characterized for floating ability, compatibility study, particle size and shape, entrapment efficiency, in-vitro drug release. Due to their low density, these multi particulate drug delivery systems showed good floating ability and remained in gastric environment for more than 24 hrs, required for sustained therapeutic activity. Major advantages of the system include ease of preparation, good floating ability, high encapsulation efficiency and sustained drug release over 24 hours. From this study, it was concluded that formulation of floating microspheres of ofloxacin offers prolonged gastric residence time and continuous release of the medication over an extended period of time thus oral bioavailability of the drug and subsequent efficacy is improved.

Recent Advance in Gastroretantive Drug Delivery System (GRDDS)

The drug delivery system is most important and preferable drug delivery system. This route has high patient acceptability, primarily due to easy of administration. Effective oral drug delivery depends upon the factors such as gastric emptying process, the gastrointestinal transit time of the dosage form drug release from the dosage form, and site of absorption of drug. In recent years, scientific and technological advancements have been made in the research and development of gastro retentive drug delivery systems. Hence forth a wide spectrum of dosage forms has been developed for the drugs which have narrow absorption window, unstable at intestinal pH, are soluble in acidic pH, and have a site of action specific to stomach. The purpose of writing this review was to investigate, compile and present the recent as well as past literature in a more concise way with a special focus on approaches that are currently utilized in the prolongation of gastric residence time. These include floating system, swelling and expanding system, bio/mucoadhesive system, high-density system, and other delayed gastric emptying devices. The present review addresses briefly the classification, formulation consideration for Gastroretantive drug delivery system (GRDDS), factors controlling gastric retention, merits, demerits, and applications of gastro retentive drug delivery systems.

The development and optimisation of gastro-retentive floating tablets using fused deposition modelling 3D printing.

To develop a robust tablet design for the manufacture of gastro-retentive tablets using fused deposition modelling three-dimensional printing (FDM-3DP) that can provide prolonged gastric residence time with instant floating and minimum influence of process and/or formulation variables. Three different polymers, such as polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC) and Soluplus were used, separately, for the manufacture of tablets using FDM-3DP. Tablets were designed in a sandwich model that included voids in the internal structure to support buoyancy. Fabricated tablets from all polymers were instantly buoyant with no floating lag time. Floating duration was in the order: HPC > Soluplus > PVA which can be explained by the density of the tablets. PVA tablets exhibited significantly (P < 0.05) higher density values (0.86±0.02mg/mm3) than HPC and Soluplus (0.69±0.03 and 0.72±0.02mg/mm3, respectively). HPC and Soluplus showed similar zero-order drug release profiles (f2 > 50) and were able to sustain the release of theophylline for 12h, whereas complete drug release was achieved from PVA tablets after 3h. Robust gastro-retentive tablets that show instant buoyancy regardless of the polymeric carrier type and composition were successfully manufactured utilising FDM-3DP. This allows for overcoming the restrictions posed by process/formulation parameters on the floatability of gastro-retentive tablets.

Formulation And Evaluation Of Floating Microspheres Of Cefdinir

Various approaches have been used to retain the dosage form in the stomach as a way ofincreasing the gastric residence time (GRT), including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extendible, or swellable systems; andsuperporous hydrogel systems. The aim of this study was to prepare and evaluate floatingmicrospheres of cefdinir for the prolongation of gastric residence time. Themicrospheres were prepared byCapillary Extrusion method.A full factorial design was applied to optimize the formulation. The optimum batch of microsphere exhibited smooth surfaces with good flow and packing properties, prolonged sustained drug release, remained buoyant for more than 12 hrs, high entrapment efficiency upto68%.Scanning electron microscopy confirmed the hollown structure with particle size in the order of190 μm. The studies revealed that increase in concentration of gum Karaya increased the drug release from the floating microspheres.

Development of a furosemide-containing expandable system for gastric retention

More than 50 years ago, the first gastroretentive dosage forms came up. Since then, no practical and at the same time reliable gastroretentive system is available on market. A major obstacle in the development of novel gastroretentive systems is the lack of proper predictive test methods. In the present work, we aimed at developing and fully characterizing an expandable gastroretentive system containing furosemide as model drug. On the one hand, we used well-established in vitro tests for drug dissolution and gastroretentive properties (paddle apparatus, swelling characteristics). On the other hand, we used two novel models (dissolution stress test device, mechanical antrum model) to assess these properties under biorelevant conditions. Moreover, we performed an in vivo study under fed and fasted conditions that combined blood sampling and a high-resolution imaging technique (magnetic marker monitoring) to determine gastrointestinal location with the assessment of a pharmacodynamic endpoint (urinary sodium excretion). In vitro dissolution tests confirmed prolonged drug release over more than 8 h independent from pH and with slight pressure sensitivity. Swelling studies indicated good swelling behavior within 4 h along with medium gastroretentive properties as determined with the mechanical antrum model. In vivo imaging showed prolonged gastric residence time after fed compared to fasted administration (481 min vs 38 min). Comparison of geometric means of AUCo-tlast of the model drug confirmed this observation with 10 times higher value after fed administration. Urinary excretion of sodium well reflected the increased sodium-reuptake inhibition due to higher furosemide exposure under fed conditions.However, the poor performance after fasted intake of the system is in line with data from several other gastroretentive formulations. The present study highlighted the value of novel test methods during the development of gastroretentive formulations. Yet, a system with reproducible gastroretentive properties especially under fasted conditions has to be designed.

Process Optimization for the Continuous Production of a Gastroretentive Dosage Form Based on Melt Foaming

Several drugs have poor oral bioavailability due to low or incomplete absorption which is affected by various effects as pH, motility of GI, and enzyme activity. The gastroretentive drug delivery systems are able to deal with these problems by prolonging the gastric residence time, while increasing the therapeutic efficacy of drugs. Previously, we developed a novel technology to foam hot and molten dispersions on atmospheric pressure by a batch-type in-house apparatus. Our aim was to upgrade this technology by a new continuous lab-scale apparatus and confirm that our formulations are gastroretentive. At first, we designed and built the apparatus and continuous production was optimized using a Box–Behnken experimental design. Then, we formulated barium sulfate-loaded samples with the optimal production parameters, which was suitable for in vivo imaging analysis. In vitro study proved the low density, namely 507 mg/cm3, and the microCT record showed high porosity with 40 μm average size of bubbles in the molten suspension. The BaSO4-loaded samples showed hard structure at room temperature and during the wetting test, the complete wetting was detected after 120 min. During the in vivo study, the X-ray taken showed the retention of the formulation in the rat stomach after 2 h. We can conclude that with our device low-density floating formulations were prepared with prolonged gastric residence time. This study provides a promising platform for marketed active ingredients with low bioavailability.

IN VITRO IN VIVO STUDIES ON FLOATING MICROSPHERES FOR GASTRORETENTIVE DRUG DELIVERY SYSTEM: A REVIEW

The purpose of writing this review on gastroretentive drug delivery systems (GRDDS) was to compile the recent literature with a special focus on various gastroretentive approaches that have recently become leading methodologies in the field of site-specific orally administered controlled release drug delivery. One of the complex processes in the human body is gastric emptying, as it is highly variable, which makes the in vivo performance of the drug delivery systems uncertain. GRDDS has gained immense popularity in the field of oral drug delivery recently. It is a widely employed approach to retain the dosage form in the stomach for an extended period of time and release the drug slowly that can address many challenges associated with the conventional oral delivery system. Conventional drug delivery systems may not overcome the issues imposed by the gastrointestinal tract (GIT) such as incomplete release of drugs, decrease in dose effectiveness, and frequent dose requirement. To overcome this variability, a controlled drug delivery system with a prolonged gastric residence time of &gt;12 h in the stomach can be of great practical importance for drugs with an absorption window in the upper small intestine. GRDFs enable prolonged and continuous release of the drug to the upper part of the GIT and thus significantly extend the duration of drug release and improve the bioavailability of drugs that have a narrow therapeutic window; by this way, they prolong dosing interval and increase compliance.

Development and Evaluation of Gastrobioadhesive Glimepiride Sustained Release Matrix Tablet Using Aegle Marmelos Polysaccharide

The purpose of present study was to formulate and evaluate glimepiride gastrobioadhesive drug delivery using Aegle Marmelos polysaccharide and synthetic polymer for prolongation of gastric residence time and reduce the dosing frequency. Glimepiride matrices were prepared by direct compression method and evaluated with an aim of presenting glimepiride as sustained release for improving the patient’s compliance. A central composite design (CCD) was employed as Aegle Marmelos polysaccharide (X1) and HPMC K4M (X2) independent variables to optimize the glimepiride in terms of sustained release and gastrobioadhesive. The response (Y1) as bioadhesive strength, (Y2) percentage drug releases at 8 h and (Y3) time (t50) required to 50% drug release were measured for each trial and statistical equations with significant interaction terms were derived to predict relation. The physical properties of all formulations hardness, friability, drug content and weight variation were found within limits indicating that the prepared matrix tablets met the USP specifications. Among all the formulations, F1 formulation found to be optimized based on the criteria of attaining the maximum value of drug released Q8 of 98.58±1.12%, 18.43 g bioadhesive strength and time to 50% drug release (t50) of 6 h. An in-vitro drug release studies reveals that as concentrations of polymers increases the drug release decreases, producing sustained release of glimepiride. The release co-efficient values ‘n’ (˂0.3645) indicated that the drug release (F1) followed fickian diffusion mechanism kinetics. A glimepiride gastroadhesive matrix was developed to enhance its bioavailability by prolonging the gastric residence time with desirable release modulation for a once daily administration.

Development and Evaluation of Microballons Based Extended Release Drug Delivery System for Hypertension Therapy

The objective of the present work was to formulate and evaluate micro balloons of Captopril to for prolongation of gastric residence time. The micro balloons were prepared by the solvent diffusion technique using different ratio of Ethyl cellulose, HPMCK4M &amp; acrylic polymers as Eudragit RL100. Micro balloons characterized for micrometrics properties found in passable to good range, the yield of micro balloons was up to 71.20 ±4.68 to 92.25 ±2.34 % and % entrapment efficiency was found to be 71.40±1.64 to 87.34±2.54% respectively. The size of micro balloons formulations was in the range of 159.1±4.09 to 203.42±5.61. The shape and surface morphology of prepared micro balloons were characterized by scanning electron microscopy. The micro balloons formed were additionally found to be floating over gastric juice for &gt; 12 hours. A broad range of drug release pattern could be achieved by varying the drug and polymer amount, the best results were obtained in F-4 formulation at the ratio of drug: polymer (1:1) containing HPMC K4M and Eudragit RL100 as a polymer exhibited prolong drug release over 12 hrs. Higher values of correlation coefficients were obtained with Higuchi’s square root of time kinetic. The mechanism of the release of Captopril from formulation was found to be Non-fickian transport. Drug–Polymers interaction has been determined based on FTIR studies. Optimized formulation (F-4) was stable up to 90 days prior storage at 40±20C &amp; 5-8±20C in terms of % yield, %E.E. &amp; % drug released. Non-significant difference was observed in above analyzed parameters, supported by t crit &gt; t stat by t test with p =0.05. The developed Floating micro balloons of Captopril might be clinically used for prolonged drug release in GIT, for better drug utilization and improved patient compliance.

Floating Oral In-Situ Gel: A Review

The drugs having a narrow absorption window in the gastrointestinal tract (GIT) when administered by oral route are often limited by poor bioavailability due to incomplete drug release and short residence time at the site of absorption. Novel drug delivery systems in the form of gastroretentive systems such as floating systems, mucoadhesive, high-density, expandable have been developed as they provide controlled delivery of drugs with prolonged gastric residence time. Liquid orals are more prone to low bioavailability because they are eliminated quickly from the stomach since they are subjected to faster transit from the stomach/ duodenum. The problems of immediate release and short gastrointestinal residence of liquids are eliminated by formulating as oral in situ gels as they provide the best means to overcome these problems The in situ gel dosage form is a liquid before administration and after it comes in contact with gastric contents due to one or more mechanisms gets converted to gel which floats on gastric contents. This achieves increased residence as well as sustained release. This approach is useful for systemic as well as local effect of drugs administered. This review gives a brief idea about floating oral in-situ gel formation and research done by various scientists on a number of drugs and polymers.&#x0D; Keywords: Floating drug delivery, gastric retention time, In-situ gel.

A physiologically based pharmacokinetic model for valacyclovir established based on absolute expression quantity of hPEPT1 and its application

In this study, a physiologically based pharmacokinetic (PBPK) model was established for valacyclovir based on absolute expression quantity of hPEPT1 along the entire length of the human intestine and other reliable in vitro, in vivo observed data. The PBPK model-3 defined acyclovir as metabolite of valacyclovir and simulated the plasma concentration-time profiles of valacyclovir and acyclovir simultaneously. It was validated strictly by a series of observed plasma concentration-time profiles. The average fold error (AFE) and absolute average fold error (AAFE) values were all smaller than 2. Then, it was used to quantitatively evaluate the effect of hPEPT1, luminal degradation rate, drug release rate and gastric residence time on the oral absorption of valacyclovir and acyclovir. The PBPK model-3 suggests that mainly 75% of valacyclovir was absorbed by active transport of hPEPT1. The luminal degradation of valacyclovir in the upper intestinal lumen cannot be considered the only reason for its incomplete bioavailability. The plasma concentration-time profiles of valacyclovir and its metabolite acyclovir were not sensitive to dissolution rate faster than T85% = 120 min. Prolonged gastric residence time of sustained release tablet can improve the oral absorption of valacyclovir. All in all, the PBPK model-3 in this study is reliable and accurate. It is useful for the research of clinical application and dosage forms design of valacyclovir.

A QbD approach for the fabrication of immediate and prolong buoyant cinnarizine tablet using polyacrylamide-g-corn fibre gum

The main hurdle in the oral delivery of cinnarizine is its supersaturation, precipitation and re-dissolution process, influencing the oral bioavailability. To overcome this problem, an attempt was made to develop immediate and prolong buoyant tablet of cinnarizine. For this purpose, polyacrylamide-g-corn fibre gum (p-CFG) was synthesized as mucoadhesive cum swellable polymer and it was compared with already used HPMC K4M polymer. The central composite design with two numeric and one categorical factor was choosen to optimize conc. of p-CFG (X1), concentration of NaHCO3 (X2) and type of effervescent agents (X3). The bioadhesive strength of p-CFG tablet was 2.4 times higher than HPMC K4M containing tablet. The formulation composition comprises of p-CFG (64.3%), sodium bi‑carbonate (12.9%) and citric acid (2%) (FCNZ) fulfilled the maximum requirement of an optimized formulation. The in-vivo animal pharmacokinetic performance revealed larger plasma half-life and reduced elimination rate as compared to CNZ suspension. Interestingly, the absorption of CNZ from optimized formulation was 3 times enhanced than from CNZ suspension. Overall, the enhancement in the oral bioavailability of CNZ was evident that is due to its prolonged gastric residence time. Furthermore, the swelling associated floating followed by mucoadhesive nature of tablet was observed by X-ray imaging studies.