Reduced Dosing Frequency Research Articles

Hypogammaglobulinemia secondary to B-cell depleting therapies in neuroimmunology: Comparing management strategies.

Anti-CD20 agents are commonly used in MS, NMOSD, and MOGAD. Few studies have compared strategies to address hypogammaglobulinemia. To compare strategies to manage secondary hypogammaglobulinemia in neuroimmunology patients, including reducing anti-CD20 dose and dosing frequency, IVIG/SCIG, anti-CD20 cessation, and DMT switches. All MS, NMOSD, and MOGAD patients at our institution with hypogammaglobulinemia on anti-CD20 agents from 2001 to 2022 were analyzed. The median change in IgG, infection frequency, and infection severity before and after the treatment was calculated. In total, 257 patients were screened, and 30 had a treatment for hypogammaglobulinemia. IVIG/SCIG yielded the largest increase in IgG per year (674.0 mg/dL), followed by B-cell therapy cessation (34.7 mg/dL), and DMT switch (5.9 mg/dL). Dose reduction had the largest decrease in yearly infection frequency (2.7 fewer infections), followed by IVIG/SCIG (2.5 fewer), DMT switch (2 fewer), and reduced dosing frequency (0.5 fewer). Infection grade decreased by 1.9 for reduced dosing frequency (less severe infections), by 1.3 for IVIG/SCIG, and by 0.6 for DMT switch. This data suggests that IVIG/SCIG may yield the greatest recovery in IgG while also reducing infection frequency and severity. Stopping anti-CD20 therapy and/or switching DMTs also increase IgG and may lower infection risk.

Controlled Release Levetiracetam Loaded Eudragits Microspheres for Oral Drug Delivery: Preparation and Evaluation

This work aims to prepare controlled release microspheres loaded with levetiracetam (LEV) for oral use that will have a targeted release site, thus reducing dose frequency and improving patient compliance. Levetiracetam is a 2nd generation antiepileptic medication with a T/half-life of 7 hours that is administered twice daily, which makes it suitable for formulation that will reduce dosing intake. The microspheres were prepared by solvent evaporation method using Eudragit E100, L100, and S100 polymers as matrix core polymers at diff erent ratios 1:1, 1:2 and 1:3 with levetiracetam. These polymers have diff erent pH sensitivity profi les, which will aid the release of levetiracetam in a controlled manner along the gastrointestinal tract. The prepared microspheres were evaluated for yield percentage, entrapment effi ciency (EE%), morphological characteristics and in-vitro release profi le. The yield percentage and EE% for the formulation at diff erent ratios ranged from 69–99%. The in-vitro release analysis showed favorable targeted release of the drug at specifi c pH ranges matching specifi c sites in the gastrointestinal tract.

Preparation and Evaluation of Ophthalmic Ketorolac Tromethamine Minitablet

Objective: The current research is for improving patient compliance by reducing dosing frequency of ocular ketorolac tromethamine used for allergic conjunctivitis through preparation of minitablet for ocular insertion. Method: Ocular mini tablet was prepared by direct compression method using xanthan gum, chitosan and carbopol 943P as polymers to prepare the mini tablet for ocular insertion. The mini tablets were evaluated for drug content, weight variation, bioadhesion, water uptake and swelling behavior, in vitro drug release and ocular irritation. Results: The best formula (F1) containing 1% chitosan gave mini tablets with dimension (3 × 0.7 mm) with satisfactory physical properties and 100% release after 12 hours to be inserted anteriorly. Conclusion: This work succeeded in preparing ocular mini tablet of ketorolac tromethamine to be inserted anteriorly for the treatment of allergic conjunctivitis. As promising sustained release drug delivery system to be a good alternative for the conventional treatment regimen to improve patient compliance by reducing frequent doses with no irritation.

A Recent Advance on Transdermal Drug Delivery System

From the past three decades there are huge changes and developments in formulation technology. Innovations in drug delivery systems are not only associated with the development of novel dosage forms but also with the development of new formulations using existing drugs for the treatment. These innovations in delivery of drug have many advantages like better patient compliance, maintenance of steady state concentration of drug for the prolong period, reducing dosing frequency, drug targeting to desired site of action and low side effects. TDDS are designed for delivery of drugs across the skin and it provides both controlled and continuous administration drug. It terminates the pulsed entry of drug in systemic circulation due to which side effects are observed. This transdermal route of drug delivery has more benefits and convenience than oral route and enhances the safety and efficacy of drug; it is patient friendly and painless device that provides regulated, uniform administration and the continuous supply of drug to targeted site for treatment of various diseases.

FORMULATION AND EVALUATION OF CETIRIZINE HYDROCHLORIDE pH TRIGGED IN-SITU OCULAR GEL

Objective: In the present research work, the aim was to prepare pH trigged in-situ ocular gel of Cetirizine Hydrochloride (CTZ) to improve its local bioavailability at the eye surface. Methods: CTZ in-situ ocular gel was prepared by the pH-trigged method. In-situ CTZ ocular gel was prepared by a pH-sensitive gelling agent (Carbomer) with a one-viscosity builder polymer (HPMC E4M). All formulation was evaluated for appearance, pH, viscosity at different pH, gelling capacity, % drug content, and drug release. Nine formulations were prepared and optimized successfully using 32 factorial designs. Optimization was done by DoE software version Version 13.0.10.064. Results: All nine formulations of in-situ ocular gel were subjected to evaluation. Out of 9 formulations, F3 had a good gelling capacity with the minimum amount of polymer. The appearance of the optimized formulation was translucent and homogenous. The pH of the F3 formulation is 5.55±0.07, which is good for maintaining formulation in the solution stage. Viscosity at 20 RPM of F3 formulation at pH 5.5 is 837.30±1.00 cps; this range of viscosity has good flow properties. Viscosity at 20 RPM of F3 formulation at pH 7.4 is 6800.74±1.58cps; this range of viscosity has a good gelling capacity which helps to drug retain at the eye surface. Drug content is 100.16±0.53%. Drug release at 300 min is 69.22±2.12, it can say that the drug may be retained for more than 300 min at the eye surface, which is good for reducing dosing frequency. Conclusion: CTZ was successfully formulated in pH triggered in-situ gelling system using Carbomer 974P in combination with HPMC E4M. The prepared in-situ gel is easily converted from solution stage to gel stage at the pH of the eye so we can say that the drug in the in-situ ocular gel is more bioavailable than conventional ophthalmic solution In vitro results indicated that the in-situ gel system is a viable alternative to conventional ocular drops by virtue of its ability to sustain drug release.

Darren P. Baker, PhD A Pioneer in the Development of Pegylated Interferon-β for Clinical Use

Darren P. Baker, PhD A Pioneer in the Development of Pegylated Interferon-β for Clinical Use

Exploring patient experience and satisfaction with depot buprenorphine formulations: A mixed-methods study.

The introduction of depot buprenorphine for the treatment of opioid dependence allows for reduced dosing frequency compared with conventional treatments, such as oral methadone and sublingual buprenorphine-naloxone. Reduced dosing frequency is perceived to reduce issues such as high out-of-pocket costs, frequent attendance to pharmacies, stigmatisation and the risk of diversion for unsanctioned opioid use. This study aims to explore the experiences of patients receiving depot buprenorphine from an Australian publicly operated drug and alcohol service. Participants were recruited from the service over a 5-week period in 2021. Twenty-eight participants consented to be involved in a mixed methods quantitative verbal survey and qualitative interview process. The majority of participants reported satisfaction with depot buprenorphine across the domains of efficacy, convenience and global satisfaction. Participants perceived benefits as increased convenience, reduced stigmatisation and the inability to 'skip' daily Medication Assisted Treatment for Opioid Dependence (MATOD) doses. There were mixed experiences with the ability for depot buprenorphine to 'hold' participants throughout the dosing interval. Reduced contact and disconnection from healthcare services were reported as an issue for some participants when initiating depot buprenorphine. Patient perceptions of depot buprenorphine appear to be deeply rooted in prior experience with 'conventional' MATOD treatments. Depot buprenorphine is seen to be beneficial socially, personally, and financially by the majority of patients interviewed. The potential for disconnection from services and mixed experiences of efficacy throughout the dosing period may negatively influence patient experience.

Development of depot PLGA-based in-situ implant of Linagliptin: Sustained release and glycemic control

High percentage of diabetic people are diagnosed as type 2 who require daily dosing of an antidiabetic drug such as Linagliptin (Lina) to manage their blood glucose levels. This study aimed to develop injectable Lina-loaded biodegradable poly (lactic-co-glycolic acid) (PLGA) in-situ implants (ISIs) to deliver a desired burst effect of Lina followed by a sustained release over several days for controlling the blood glucose levels over prolonged time periods. The morphological, pharmacokinetic, and pharmacodynamic assessments of the Lina-loaded ISIs were performed. Scanning electron microscopy (SEM) study revealed the rapid exchange between the water miscible solvent (N-methyl-2-pyrrolidone; NMP) and water during the ISI preparation, hence enhancing the initial burst Lina release. While, triacetin of lower water affinity could lead to formation of more compact and dense ISI structure with slower drug release. By comparing various ISI formulations containing different solvents and different PLGA concentrations, the ISI containing 40 % PLGA and triacetin was selected for its sustained release of Lina (93.06 ± 1.50 %) after 21 days. The pharmacokinetic results showed prolonged half life (t1/2) and higher area under the curve (AUC) values of the selected Lina-loaded ISI when compared to those of oral Lina preparation. The single Lina-ISI injection produced a hypoglycemic control in the diabetic rats very similar to the daily oral administration of Lina after 7 and 14 days. In conclusion, PLGA-based ISIs confirmed their suitability for prolonging Lina release in patients receiving long-term antidiabetic therapy, thereby achieving more enhanced patient compliance and reduced dosing frequency.

Leveraging Physiologically Based Modelling to Provide Insights on the Absorption of Paliperidone Extended-Release Formulation under Fed and Fasting Conditions.

Paliperidone was approved by the US FDA in 2006 as an extended-release (ER) tablet (Invega®) for the once-daily treatment of schizophrenia. This osmotic-controlled release oral delivery system (OROS) offers advantages, such as the prevention of plasma concentration fluctuation and reduced dosing frequency. The administration of the ER after a high-fat/high-calorie meal leads to increased maximum plasma concentration and area under the curve values by 60% and 54%, respectively. Food has various effects on gastrointestinal (GI) physiology, including changed transit times, changed volumes, altered pH in different GI compartments, secretion of bile salts, and increased hepatic blood flow. This may affect solubility, the dissolution rate, absorption, and the pharmacokinetics. The aim of this study was to apply physiologically based absorption modeling (PBAM) to provide insights on paliperidone ER absorption under fed and fasting conditions. The PBAM adequately predicted absorption from the OROS formulation under both conditions. Absorption primarily occurs in the ascending colon and caecum. After a high-fat/high-calorie meal, absorption is increased through the jejunum, ileum, and colon due to either increased solubilization or the better efficiency of the OROS technology. PBAM-guided approaches can improve the understanding of branded drugs and thereby aid in guiding the development of generic formulations or formulation alternatives.

FORMULATION AND EVALUATION OF DICLOFENAC TOPICAL GEL WITH ANALGESIC ACTIVITY

The present investigation is concerned with formulation and Evaluation of Diclofenac topical gel an anti-inflammatory, analgesic drug to circumvent the first pass effect and to improve its bioavailability with reduction in dosing frequency and dose related side effects. The diclofenac gel were prepared by using different concentration of different polymers. Six formulations were developed with varying concentrations of polymers like Carbopol, HPMC. The gels were tested for clarity, homogeneity, washability, spreadabiliy, PH, percentage drug content, skin irritation, permeability studies. From the study it was concluded that HPMC gel containing diclofenac sodium showed good consistency, homogeneity, spreadability, washability and permeability and has wider prospect for topical preparations as compared to Carbopol gel containing diclofenac sodium.

BOX-BEHNKEN DESIGN FOR OPTIMIZATION OF FORMULATION VARIABLES FOR CONTROLLED RELEASE GASTRORETENTIVE TABLET OF VERAPAMIL HYDROCHLORIDE

Objective: To develop a Verapamil hydrochloride controlled release gastro-retentive (CRGR) tablet for once-daily dosing using the response surface Box-Behnken Design (BBD) approach for the improvement of bioavailability and reduction in dosing frequency to overcome the issues related to the conventional tablet formulation. Methods: For the optimization, 33Box-Behnken design was used. The independent variables were selected, the amount of Compritol 888 ATO (A), HPMC K15M (B), and Sodium bicarbonate (C). The dependent variables were Cumulative % drug release in 1.5 h (Q1.5), 8 h (Q8), 24 H (Q24) and floating lag time (FLT). Flow properties of pre-compressed powder, physical characteristics, drug content, floating lag time, total floating time and in vitro dissolution study of all formulation were assessed. In vitro dissolution study of optimized formulation that was prepared experimentally was performed and compared with predicted data obtained from the software. Drug release kinetics of the optimized formulation was also assessed to know the mechanism of drug release from the CRGR tablets. Results: Responses of experimental runs were found as Q1.5: 12.78-33.62 (%), Q8: 43.03-64 (%), Q24: 78.77 to 103.57 (%) and floating lag time as 3.01 min to 5.08 min. The predicted optimized formula with the highest desirability value of 0.963 containing amount 126.030 mg, 160.00 mg and 80.955 mg of Compritol 888 ATO, HPMC K15M and Sodium biarbonate respectively was prepared and evaluated. The experimental values from optimized formulation were obtained as Q1.5: 23.397%, Q8; 57.744%, Q24: 97.150% and FLT: 3.12 min. Predicted and experimental results were found comparable for all the responses. The release data from the optimized formulation were best fitted in the Higuchi (r2 = 0.999) and the Korsmeyer-Peppas ((r2 = 0.998, n=0.54) model. The in vitro drug release studies indicated that the Verapamil hydrochloride gastroretentive tablet releases the drug in controlled manner for 24 h. Conclusion: This study found that using Box-Behnken Design with the response and variable relation, it is possible to achieve an optimum formulation with desirable characteristics. This study also established the suitability of Compritol 888 ATO-HPMC K15M combination with Sodium bicarbonate to increase the gastric residence time tablet formulation had once-daily dosing of the Verapamil Hcl with improved bioavailability for effective management of hypertension.

Advances in microneedle patches for long-acting contraception

Despite the advances in contraceptives, there is still a high rate of unintended pregnancies worldwide, due in large part to the lack of effective, convenient, and safe birth control methods. Compared with short-acting contraceptives, approaches that offer long-term pregnancy protection have attracted greater interest because of the reduced dosing frequency and improved patient compliance. As a novel transdermal drug delivery system, the microneedle (MN) patch has been widely used for a variety of biomedical applications, including long-acting contraception, due to unique properties, such as painless self-administration and elimination of biohazardous waste. In this review we provide a systemic review of MN patches that have been utilized for long-term contraception, including dissolvable MN patches, polymeric biodegradable MN patches, and silk fibroin-based biodegradable MN patches. The acceptability and biosafety of these contraceptive MN patches are also discussed. Finally, we give our perspectives on the future clinical translation of MN patches for long-acting contraception.

Formulation And Evaluation Of Emulgel Of An Antifungal Drug For Topical Drug Delivery

Topical drug delivery system improved bioavailability, reduced side effects, more uniform plasma levels, longer duration of action, resulting in a reduction in dosing frequency and improve therapy due to plasma levels up to the end of the dosing interval compared to a decline in plasma levels with conventional oral dosage form. Emulgel are generally used where the other systems of drug administration fails to directly treat cutaneous disorders such as fungal infections, acne, psoriasis etc.
 Materials and methods: Fluconazole emulgel was optimized based on Design-Expert® software using central composite design (CCD) making Fourteen formulations using jojoba oil and liquid paraffin, Methylparaben, Propylparaben and Triethanolamine.
 Results and Discussions: - The spreadability test range find from 8.9 g.cm/min to 14.87 g.cm/min for the formulations F1 and F14, respectively. Formulations having low amount of jojoba oil and liquid paraffin had the high spreadability index. As the viscosity of the gel increased, the release of the drug was expected to be slower. Complete drug release (100%) was achieved at the 3rd hr for the formulations F1, F8, F7 and F14 released more than 80 % of the drug and in vitro results showed that an emulgel formulation can be a potential candidate for the delivery of fluconazole for the skin disease, with better in vitro physical, using jojoba oil and liquid paraffin as drug carriers. SEM analysis of emulgel shows the uniform structure of emulgel formulation.

Phosphatidylcholine (PCL) fortified nano-phytopharmaceuticals for improvement of therapeutic efficacy.

Phytopharmaceuticals, derived from plants, are increasingly recognized for their potential therapeutic benefits. However, their effectiveness is often hindered by challenges such as poor bioavailability, stability, and targeted delivery. In this study, we aimed to address these limitations by developing PCL (phosphatidylcholine) fortified nano-phytopharmaceuticals to enhance therapeutic efficacy. PCL, a biocompatible and biodegradable polymer, was employed to encapsulate the phytopharmaceuticals, thereby improving their stability and bioavailability. The encapsulation process utilized nanoprecipitation, resulting in the formation of nanoparticles with controlled size and morphology. Various analytical techniques were employed to characterize the physicochemical properties of PCL fortified nano-phytopharmaceuticals, including dynamic light scattering, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Furthermore, the release kinetics of encapsulated phytopharmaceuticals from PCL nanoparticles were evaluated, demonstrating sustained and controlled release profiles, essential for prolonged therapeutic effects. Cytotoxicity studies conducted on in vitro cell culture models confirmed the biocompatibility and non-toxic nature of the developed nano-phytopharmaceuticals. Additionally, in vivo studies were conducted to assess the therapeutic efficacy of PCL fortified nano-phytopharmaceuticals in animal models. The results showIased improved bioavailability, targeted tissue distribution, and enhanced therapeutic effects compared to free phytopharmaceuticals. Moreover, the developed nano-phytopharmaceuticals exhibited prolonged circulation time in the bloodstream, enabling improved drug delivery and reduced dosing frequency. This review highlights the promising potential of PCL fortified nano-phytopharmaceuticals as an effective approach for enhancing the therapeutic efficacy of phytopharmaceuticals. The improved stability, bioavailability, sustained release, and targeted delivery achieved through this formulation strategy offer promising opportunities for advancing plant-based therapies. See also the Graphical abstract(Fig. 1).

Formulation and evaluation of sustained releasedomperidone hydrochloride transdermal patches to treat motion sickness

Objective: Transdermal route of drug delivery is superior than oral route because it avoids first pass effect, ensures better patient compliance, reduce dosing frequency especially in extended-release formulation and is easy to use. Domperidone HCl is DA2 receptor antagonistic and is used to prevent nausea and vomiting. The objective was to formulate a domperidone HCl extended-release transdermal drug delivery system to treat motion sickness. Methods: Five different formulations were formed using different solvents (methanol and dichloromethane) and polymers (HPMC and Eudragitl-100) by solvent evaporation method. 500mg of domperidone HCl was added in each patch and dibutyl phthalate was added as plasticizer. A 3% w/v PVA layer was used as backing. All these formulations were evaluated for their physicochemical properties (weight variation, thickness, folding endurance and tensile strength), in-vitro drug release, drug contents determination, any incompatibility between drug and excipients by FTIR and DSC and skin irritation. Results: All formulations exhibited good physicochemical properties and percentage drug release during 24 hours was 79.3%, 97.1%, 96.8%, 74.7% and 59.7% respectively. F-YM showed maximum in-vitro drug release. The optimized formulation (F-YM) followed Korsmeyer Peppas release model with n=0.383 showing that the system was following dissolution dependent drug release. No interaction between drug and excipients was detected by DSC and FTIR. No skin irritation was detected. Conclusion: The extended release transdermal patches of domperidone HCl to treat motion sickness were prepared and formulation F-YM showed optimized behavior with maximum in vitro drug release.

Formulation and In-Vitro Evaluation of Sustained Release Pilocarpine Ocuserts Using Modified Karaya Gum Extracted from Sterculia urens

Ocular inserts of Pilocarpine nitrate (PN) were prepared using modified karaya gum (MKG) alone as release retarding polymer and in combination with the copolymer sodium alginate. Modification of the karaya gum was done by treating it with the trisodium trimetaphosphate (STMP) by cross linking method and evaluated for its physicochemical properties. Films of the MKG were prepared by employing solvent casting method using varying concentrations (600mg, 500mg and 400mg) of MKG and the sandwiching technique was used for the loading of drug. Sodium alginate (SA) and PN blend were prepared by triturating their appropriate amounts. Six ocusert formulations (F1-F6) were prepared with different concentrations of the polymer i.e MKG and SA while the amount of PN was kept constant in formulations. Formulations F1-F3 contained the MKG alone in varying concentrations (600mg, 500mg and 400mg) and F4-F6 contained SA (0.5 mg) in addition to MKG. The surface pH of prepared ocuserts from the formulations (F1-F6) was in the range of 6.63 to 6.8. Thickness range of the ocuserts was from 0.21 to 0.32 mm. Dissolution profiles of prepared ocuserts were studied and drug release was found within the range of 69.2± 1.36 % (F4, minimum) to 90.5± 3.21% (F3, maximum). Overall results of the study concluded that ocuserts fabricated with MKG and SA at optimized concentrations have the potential to sustain the release of PN and therefore reducing dosing frequency and adverse effects.

Preparation and Characterization of Hydrogel Beads for Controlled Release of Amoxicillin

Amoxicillin trihydrate-loaded hydrogel beads were prepared and characterized as a controlled drug delivery system to improve patient compliance. An ionotropic gelation process was used to prepare the hydrogel beads using calcium chloride (CaCl2) as a crosslinking agent. The effects of CaCl2, sodium alginate, poloxamer 407 (PL) concentration, and preparation temperature were investigated. Spherical hydrogel beads were obtained with high encapsulation efficiency (85.74±1.09) %. FTIR analyses confirmed the compatibility of amoxicillin with the used excipients. In vitro swelling and cumulative drug release studies were performed over 24 hours in HCl medium, pH 1.2. Prepara-tion temperature was found to influence both the index of beads swelling (SI) and the cumulative release of amoxicil-lin. The study demonstrated the capability of PL to enhance the cumulative release of amoxicillin, correlating with swelling behavior. The proposed hydrogel beads have the potential as a promising drug delivery system for controlled release of amoxicillin, over 24 hours, and thus reduced dosing frequency.

Model-Informed drug development of gastroretentive release systems for sildenafil citrate

Gastroretentive drug delivery systems (GRDDS) are modified-release dosage forms designed to prolong their residence time in the upper gastrointestinal tract, where some drugs are preferentially absorbed, and increase the drug bioavailability. This work aimed the development of a novel GRDDS containing 60 mg of sildenafil citrate, and the evaluation of the feasibility of the proposed formulation for use in the treatment of pulmonary arterial hypertension (PAH), for once a day administration, by using in silico pharmacokinetic (PK) modeling and simulations using GastroPlusTM. The Model-Informed Drug Development (MIDD) approach was used in formulation design and pharmacokinetic exposure prospecting. A 22 factorial design with a central point was used for optimization of the formulation, which was produced by direct compression and characterized by some tests, including buoyancy test, assay, impurities, and in vitro dissolution. A compartmental PK model was built using the GatroPlusTM software for virtual bioequivalence of the proposed formulations in comparison with the defined target release profile provided by an immediate release (IR) tablet formulation containing 20 mg of sildenafil administered three times a day (TID). The results of the factorial design showed a direct correlation between the dissolution rate and the amount of hydroxypropyl methyl cellulose (HPMC) in the formulations. By comparing the PK parameters predicted by the virtual bioequivalence, the formulations F1, F2, F3 and F5 failed on bioequivalence. The F4 showed bioequivalence to the reference and was considered the viable formulation to substitute the IR. Thus, GRDDS could be a promising alternative for controlling the release of drugs with a pH-dependent solubility and narrow absorption window, specifically in the gastric environment, and an interesting way to reduce dose frequency and increase the drug bioavailability. The MIDD approach increases the level of information about the pharmaceutical product and guide the drug development for more assertive ways.

Preparation and characterization of crosslinked starch-albumin films for coating of prednisolone tablets for use in Covid-19 related respiratory disease

Steroidal products have been found useful in inflammations associated with Covid 19. Prednisolone is one readily available steroid, which is often found as uncoated normal release tablets. Modified release prednisolone may be desirable in Covid 19 for sustained actions. This is expected to reduce dosing frequency and enhance compliance. This study is concerned with development of controlled release prednisolone using coating technology with bio-compatible, cross-linked starch-albumin films. Starches and proteins are excellent film formers with good flexibility, transparency, and bio-compatibility. The cross-linked starch-albumin films were prepared using glycerol as the plasticizer: starch (A), starch-albumin (B), starch-albumin cross-linked with formaldehyde at 1 % (C), 5 % (D) and 10 % (E). Equilibrium moisture sorption (EMS) at 100 % relative humidity, equilibrium swelling (ESC) in buffer solutions of pHs 2, 7 and 9, and DSC thermal properties were evaluated. In-vitro drug release from the film coated prednisolone tablets were evaluated in 0.1N HCl, water and phosphate buffer 8.0 as dissolution media. Films showed ESC in the order A>D>E>B>C; D>C>A>E>B and A>D>C>B>E in acidic, neutral and alkali media respectively. EMS was in the order B>E>A>D>C; with slight shift in the melting temperatures. In-vitro release at 240 min varied from 78 to 117 % (E>D>C>A>B); 19 to 60 % (D>B>C>E>A) and 49 to 60 % (B>A>C>D>E) in 0.1N HCl, water and PBS respectively. Cross-linking improved the stability and swelling of films. The in-vitro release in alkaline medium suggests their usefulness for controlled drug delivery. New pH-responsive polymers, with improved physicochemical properties for coating prednisolone tablets were developed.

EE52 Cost-Minimisation Analysis of Ravulizumab Compared With Eculizumab in Patients With Atypical Hemolytic Uremic Syndrome (AHUS) in the Netherlands

aHUS is a rare disease characterized by a dysregulated and overactive complement system. Prior to the introduction of eculizumab, a complement C5-inhibitor, outcomes for patients with aHUS were generally poor. Eculizumab has substantially improved patient prognosis, but requires biweekly infusions that can impose a large treatment burden for patients and caregivers. Ravulizumab was designed via targeted modification of eculizumab to reduce dosing frequency to every 4 to 8 weeks, with an immediate, complete and sustained inhibition of complement C5.