Alginate-Based NDDS for Geriatric Drug Delivery Thesis

M.PHARMA THESIS · PHARMACEUTICS · 2025

NDDS Formulation of Pantoprazole, Cod Liver Oil & Calcium Citrate

Using Multiparticulated Alginate System for Geriatric Patients

Presented by: GAGAN SINGARIYA (20240471)

Supervisor: Dr. AZHARUDDIN KHAN | Co-Supervisor: Dr. NARESH KALRA

Department of Pharmacy, Lords University, Alwar, Rajasthan – 301028

CONTENTS

01

Presentation Outline

Introduction & Background

NDDS Overview

Geriatric Patients

Drug Delivery Challenges

Drug Profiles

Pantoprazole, Cod Liver Oil, Calcium Citrate

Multiparticulate System

Alginate-Based Formulation

Aims & Objectives

Research Methodology

Results Analysis

Formulation Optimization

Discussion

Conclusion & Future Scope

CHAPTER 01

Introduction

Novel Drug Delivery Systems (NDDS)

NDDS are innovative technologies for controlled drug transport, regulating rate, timing, and location of drug release.

Overcomes low bioavailability & fast metabolism

Maintains constant drug levels in bloodstream

Reduces adverse effects via site-specific delivery

Uses nanoparticles, microspheres, liposomes, hydrogels

Enhanced Bioavailability

Controlled Release

Reduced Toxicity

Improved Stability

NDDS has become an indispensable tool in contemporary pharmaceuticals — Jain et al., 2008

CHAPTER 02

Geriatric Challenges

Physiological Changes in Elderly Patients

Reduced Gastric Motility

Delayed drug absorption

Decreased Gastric Acid

Altered drug dissolution

Reduced Liver Function

Slower drug metabolism

Declined Renal Function

Reduced drug excretion

Increased Body Fat

Prolonged action of lipid-soluble drugs

Dysphagia

Difficulty swallowing tablets/capsules

Polypharmacy

Drug-drug interaction risks

Cognitive Impairment

Reduced medication adherence

DRUG PROFILE 01

Pantoprazole

Proton Pump Inhibitor

Drug Profile: Pantoprazole

C₁₆H₁₄F₂N₃NaO₄S | MW: 405.4 g/mol | Benzimidazole class PPI | White crystalline powder

Irreversibly inhibits H⁺/K⁺-ATPase on gastric parietal cells → Blocks final step of acid production → Long-lasting acid suppression

Bioavailability: 70–80% | T_max: 2–3 hrs | Half-life: ~1 hr | Metabolized by CYP2C19 & CYP3A4

GERD, Peptic Ulcers, Zollinger-Ellison Syndrome, NSAID-induced gastric damage, H. pylori (combination)

Acid-labile — requires enteric coating | Unstable in gastric pH | Alginate matrix provides gastric protection

Pantoprazole is the gastroprotective agent in this NDDS combination — essential for geriatric GI protection

DRUG PROFILES 02 & 03

Cod Liver Oil

Calcium Citrate

Nutraceutical + Mineral Supplement

Cod Liver Oil

EPA + DHA (Omega-3) | Vitamin A & D | Triglycerides & Phospholipids

Bone health | Cardiovascular protection | Anti-inflammatory | Immune support

Reduces osteoporosis risk | Lowers triglycerides | Joint & cognitive support

Susceptible to oxidation | Rancidity | Alginate encapsulation protects stability

Calcium Citrate

Calcium salt of citric acid | White odorless powder | Slightly soluble | Acid-independent absorption

Releases Ca²⁺ ions in GI tract | Supports bone mineralization | Muscle & nerve function

No gastric acid needed | Taken with or without food | Less GI side effects | Better bioavailability

Osteoporosis prevention | Bone fracture reduction | Long-term supplementation ideal

FORMULATION BASIS

Alginate System

Ionotropic Gelation Mechanism

Alginate-Based Multiparticulate System

Alginate is the cornerstone polymer enabling safe, sustained co-delivery for geriatric patients

CHAPTER 03 & 04

Aim & Methodology

To develop and optimize a multiparticulate alginate-based NDDS containing Pantoprazole, Cod Liver Oil, and Calcium Citrate for geriatric patients — achieving gastric protection, controlled release, improved stability, and better patient compliance.

Develop combined delivery system with controlled release

Formulate alginate beads via ionotropic gelation

Evaluate physicochemical properties (size, morphology)

Determine encapsulation efficiency for all 3 actives

Study in vitro drug release at pH 1.2 and pH 6.8

Assess pantoprazole protection against acid degradation

Evaluate oxidative stability of cod liver oil

Pre-formulation<br/>Studies

3² Full Factorial<br/>Design (DoE)

Ionotropic Gelation<br/>Bead Preparation

Characterization<br/>(SEM, FTIR, DSC)

In-vitro Release &<br/>Stability Studies

CHAPTER 04

Formulation Steps

Ionotropic Gelation Method

Method of Formulation

Pantoprazole Alginate Microspheres

Sodium alginate dissolved in purified water → Pantoprazole dispersed uniformly → Extruded dropwise into CaCl₂ → Gelation → Wash & Dry

Cod Liver Oil Alginate Emulsion Beads

Alginate solution + Cod Liver Oil + Tween 80 → Homogenized to oil-in-water emulsion → Extruded into CaCl₂ → Ionic cross-linking → Wash & Dry

Calcium Citrate Alginate Microspheres

Calcium citrate dispersed in alginate solution → Extruded into CaCl₂ under mild agitation → Ionotropic gelation → Wash & Dry

Blending

All three dried multiparticulate types accurately weighed → Gently blended in clean dry container → Visual inspection for uniformity

Encapsulation

Optimized blend filled into hard gelatin capsules → Manual filling technique → Visual inspection → Stored in airtight containers

Key Materials

Pantoprazole

(API)

Cod Liver Oil

(Nutraceutical)

Calcium Citrate

(Mineral)

Sodium Alginate

(Polymer)

CaCl₂

(Cross-linker)

Tween 80

(Surfactant)

CHAPTER 05

Results

Particle Size & Entrapment Efficiency

Key Results — Particle Size & Entrapment Efficiency

660–820 µm

Particle Size Range

Decreased with higher X1, X2, X3 levels — compact uniform beads

68.5–81.5%

Entrapment Efficiency

Increased with polymer concentration — denser matrix reduces drug leakage

Higher alginate (X1)

More compact gel network

Smaller, uniform beads

Higher CaCl₂ (X2)

Stronger ionic cross-linking

Better structural integrity

Higher stirring (X3)

Better droplet dispersion

Reduced aggregation

CHAPTER 05

Results

Release Profiles

Release Profiles & Encapsulation Performance

Pantoprazole

65–78.2%

Sustained release behavior — decreasing trend with increasing factor levels. Dense matrix reduces porosity & diffusion rate. Controlled release over 12+ hours.

Cod Liver Oil

72.1–85%

Progressive increase with higher X2 & X3. CaCl₂ × Stirring interaction = strong synergistic effect. Alginate encapsulation protects omega-3 from oxidation.

Calcium Citrate

62.4–78.5%

Gradual diffusion-controlled release. Sustained ion release suitable for long-term supplementation. Denser cross-linking → better sustained release.

Optimized Formulations: Runs 20 & 21 — Best balance of Particle Size (660–680 µm) | EE (80.2–81.5%) | Oil Entrapment (83.7–85%) | Drug Release (65–66.8%)

CHAPTER 05

DoE Optimization

3² Full Factorial Design

Effect of Formulation Variables (DoE Analysis)

X₁: Alginate Conc.

Particle Size (820→680 µm)

EE (70→80%)

Drug Release (76→67%)

Oil Entrapment (73→83%)

Ca Release (64→76%)

Most dominant factor

X₂: CaCl₂ Conc.

Particle Size (760→720 µm)

EE (73→77%)

Drug Release (74→70%)

Strong effect on bead rigidity & ionic cross-linking density

X₃: Stirring Conditions

Particle Size (780→740 µm)

EE (73→77%)

Drug Release (74→70%)

Better droplet dispersion & bead uniformity

Run 21

81.5

65.0

85.0

660

Best (88)

Run 20

80.2

66.8

83.7

680

Excellent (85)

Run 26

76.4

72.0

80.2

730

Good (82)

Predicted vs Observed values showed minimal deviation — confirms high accuracy and robustness of regression model (R² > 0.99)

CHAPTER 06

Discussion

Discussion of Key Findings

Particle Size

Findings align with Fazal et al. (2023) — increased alginate concentration produces compact microspheres via stronger ionic gel formation. Bhattacharya et al. (2019) confirmed higher stirring reduces aggregation. Particle size range 660–820 µm confirms oral suitability.

Entrapment Efficiency

Singh et al. (2017): Higher alginate improves matrix viscosity, minimizing drug diffusion. Rao et al. (2019): Calcium cross-linking improves matrix integrity. EE 68.5–81.5% confirms efficient drug loading for all three actives.

Drug Release & Oil Entrapment

Gupta et al. (2019): Dense hydrogel networks control diffusion. Dave et al. (2020): Increased cross-linking reduces permeability. Oil entrapment 72.1–85% — alginate effectively stabilizes lipophilic cod liver oil, confirmed by Nair et al. (2020).

Optimization

Runs 20 & 21 match desirability-based outcomes reported by Rafati et al. (2011). Minimal deviation between predicted and observed values confirms model robustness. Statistical models showed excellent R² values supporting reliable optimization.

Overall findings are in close agreement with published literature — validating the multiparticulate alginate system for combined geriatric drug + nutraceutical delivery

CHAPTER 07

Conclusion

Conclusion

Successful Development

Multiparticulate alginate beads successfully formulated containing Pantoprazole, Cod Liver Oil & Calcium Citrate via ionotropic gelation — simple, economical and reproducible.

Optimized Formulation

Runs 20 & 21 identified as best performers: EE 80.2–81.5%, Oil Entrapment 83.7–85%, Particle Size 660–680 µm, Drug Release 65–66.8% — controlled & sustained.

Gastric Protection

Alginate matrix effectively protected acid-labile pantoprazole from gastric degradation — confirmed by in vitro studies at pH 1.2.

Nutraceutical Encapsulation

Cod liver oil encapsulated with 72.1–85% efficiency — alginate protects omega-3 fatty acids from oxidative degradation.

Patient Compliance

Single oral multiparticulate capsule combines gastroprotection + nutrition + calcium — reducing pill burden for geriatric patients.

Future Scope

In-vivo pharmacokinetic studies, SEM/FTIR/DSC characterization, and scale-up manufacturing recommended for clinical translation.

This NDDS platform represents a promising approach for comprehensive geriatric therapy — combining pharmaceutical and nutraceutical delivery in one system.

Thank You

Questions & Discussion Welcome

Gagan Singariya | 20240471 | M.Pharma Pharmaceutics | 2025

Key References

Dhasmana et al. (2024) — Alginate hydrogel beads with anti-aging properties. Scientific Reports.

Arafat et al. (2023) — Enteric-coating film effect on pantoprazole. F1000Research.

Elsebaie et al. (2022) — Cod liver oil encapsulation in alginate beads. Foods.

Yadav et al. (2020) — Floating beads of Ketoprofen & Pantoprazole. Int J Appl Pharm.

Pereira et al. (2021) — Lansoprazole in sodium alginate beads. J Pharm Pharmacol.

Pandey et al. (2011) — Floating beads of pantoprazole sodium. Int J Pharm.

George & Abraham (2006) — Alginate & chitosan for drug delivery. J Controlled Release.

Sriamornsak & Kennedy (2008) — Calcium polysaccharide gels. Int J Pharmaceutics.

Tapia et al. (2004) — Chitosan-alginate systems for controlled release. Eur J Pharm Biopharm.

Anal & Stevens (2005) — Alginate multilayer beads. Int J Pharmaceutics.

Full reference list available in the thesis document — Department of Pharmacy, Lords University, 2025