Pharmaceutical Ice Cream-Type Formulation for Pediatric Analgesic

Abstract

Pharmaceutical Ice Cream-Type Formulation for Pediatric Analgesic The present invention pertains to a pharmaceutical formulation designed for use in pediatric dentistry. Specifically, it introduces an innovative ice cream-based analgesic formulation aimed at enhancing patient compliance and cooperation during dental procedures. This formulation provides a child-friendly delivery system that ensures controlled drug release, effectively reducing stress and discomfort. It is composed of a biocompatible base, a therapeutic agent, stabilizers, flavour enhancers, and optional nutritional additives, ensuring safety, efficacy, and appeal. By integrating analgesic properties into a child-loving medium, the formulation fosters a positive, interactive environment, encouraging cooperative behavior in pediatric dental patients.

Description

1. Technical Field of Invention:The present invention relates to the field of pediatric pharmaceutical formulations,and more particularly to a vegan, non-cariogenic ice-cream-type dosage form foranalgesic delivery in children. When specifically, the invention is directed toimproving palatability and compliance in pediatric analgesic administration, theformulation employs the disclosed technology to provide non -cariogenicsweetened, non-dairy therapeutic vehicle suitable for use by healthcare providersand other employees involved in pediatric care. The invention further employsstabilizing and delivery-enhancing components that allow the dosage form to retaintherapeutic efficacy while improving patient acceptance. The disclosed technologyfalls within the domain of pediatric drug-delivery systems, novel dosage forms, andpharmaceutical compositions designed to reduce treatment-related discomfort inchildren.2. Background of the invention:EP1089709A1, entitled "Icecream-type pharmaceutical formulation and processfor preparing the same," discloses a soft ice-cream pharmaceutical compositionprepared by mixing egg yolk, milk, and cocoa under continuous stirring untilcomplete dissolution, followed by whipping cream to a semi-solid pulp andcombining it with the mixture in a volume ratio between 9:1 and 5:5. Theformulation further incorporates the selected drug by blending and subsequentlyprocessing the mixture in an ice-cream maker to obtain a pharmaceuticallyacceptable product. This prior art teaches improved palatability and enhancedabsorption efficiency during oral administration, making the soft ice-creamformulation suitable as a child-friendly alternative to conventional troches.Thisprior-art invention, originally filed under WO2000061110, has subsequently beenfiled, withdrawn, or ceased in multiple jurisdictions, including EP1089709,CN1300208, and AU2000041465, indicating that the earlier applications are nolonger in force in these territories.A non-patented literature titled "An Ice-Cream Type Pharmaceutical Formulationof Piperazine Hydrate and Its Evaluation" describes an ice-cream-based excipientsystem composed of milk, skimmed milk powder, solid-not-fat content, sugar,sodium alginate, mono-triglycerides, emulsifying cream or butter, flavoring agents,and water. These components formed an oil-in-water emulsion into whichpiperazine hydrate was incorporated. Three drug-to-base ratios (1:9, 2:8, 3:7) wereevaluated, with 1:9 showing the closest resemblance to standard ice cream.Diffusion studies showed minimal release in acidic pH (23.5% at 2 hours) and rapidrelease in alkaline pH (≈80% in 15 minutes). Stability testing showed 93.4% drugretention after three weeks of refrigeration.The non-patented literature titled "Physicochemical, sensory and antimicrobialproperties of the ice cream containing lavender (Lavandula angustifolia) essentialoil" examines the effects of adding lavender essential oil (LEO) to ice cream at 0-0.1%. The study evaluates physicochemical, rheological, colorimetric, sensory, andantimicrobial properties. LEO incorporation reduced melting rate and increasedoverrun (P<0.05). The control sample showed the highest sensory score, while colorand viscosity varied with LEO concentration. All samples demonstratedpseudoplastic flow. Antimicrobial analysis revealed that LEO addition reducedonly S. aureus ATCC 29213, with no significant effect on L. monocytogenes ATCC7644.A non-patented literature titled "Preparation of Ibuprofen as Pediatric Candies"outlines ibuprofen-loaded gelatin candies formulated with bovine gelatin, glycerol,sucrose, flavoring agents, methyl paraben, and phosphate buffer (pH 7.2). Gelatinbases of 5%, 6%, and 7% were tested, with 6% selected. Each candy contained 100mg ibuprofen, showing >80% dissolution within 30 minutes and good stability at40°C / 75% RH over 12 weeks. Drug-to-base ratios of 1:9, 2:8, and 3:7 wereevaluated, with 1:9 providing optimal characteristics. Diffusion studies showed lowrelease in acidic pH but rapid release at intestinal pH (80% in 15 minutes) with93.4% drug retention after three weeks of refrigeration.Conventional ice-cream-based pharmaceutical formulations described in prior art,including EP1089709A1 and related family applications (WO2000061110,CN1300208, AU2000041465), primarily rely on dairy-derived components such asmilk, cream, skimmed milk solids, egg yolk, and sucrose. These formulations arelimited by their allergenic potential, high lactose content, and unsuitability forchildren with egg allergy, lactose intolerance, or dairy-fat restrictions. Furthermore,sugar-rich systems increase cariogenic risk in pediatric populations, directlycontradicting modern preventive dental principles. Such dairy-based systems alsoexhibit variable fat content, inconsistent emulsification behavior, and thermallysensitive protein structures that compromise drug stability, palatability, anduniformity during freezing. As a result, earlier formulations lack universalacceptability, especially for children requiring allergen-free, non-cariogenic, andnutritionally safer drug delivery options.In parallel, non-patented literature on ice-cream or confectionery drug carriers,including piperazine-hydrate ice-cream formulations and ibuprofen gelatin candies,continue to depend on animal-derived excipients such as bovine gelatin, milkproteins, emulsifying cream, or egg-based systems. These approaches fail toaddress critical pediatric limitations such as food allergies, gastric sensitivity, fatcontent intolerance, and the rising requirement for vegan and low-cariogenic dosageforms. Moreover, no previous formulation integrates dual-drug pediatric analgesics(paracetamol + ibuprofen) into a frozen, palatable delivery matrix while ensuringuniform dispersion, physicochemical stability, and controlled freezing behavior.Existing studies also lack non-dairy emulsification strategies and do not considerthe impact of stabilizers, sweeteners, and plant-based milk matrices on drugdiffusion, viscosity, melting profile, and acceptability in children.Unlike conventional dairy-dependent formulations, the present inventionintroduces a vegan, allergen-minimized, pediatric-friendly analgesic ice-creamsystem based on almond milk, a plant-derived matrix that is naturally lactose-free,egg-free, cholesterol-free, and suitable for children with common food allergies.Almond milk, unlike coconut milk, avoids excessive fat content; unlike soy milk,it avoids phytoallergen concerns; and unlike dairy milk, it eliminates lactose andcasein intolerance risks. The formulation employs xanthan gum as a plant-basedstabilizer and xylitol as a non-cariogenic sweetener with proven anti-cariogenicbenefits, making the system uniquely compatible with pediatric dentalrequirements-an aspect completely absent in prior art.Notably, no existing pharmaceutical formulation exist which integrates crudeparacetamol, crude ibuprofen, or their combination into a frozen almond-milkmatrix, nor does any prior art provide a method for achieving consistent drugdispersion, homogenization stability, and freezing behavior in a vegan base. Theuse of almond milk as a pharmaceutically functional excipient, not merely as a foodingredient, represents an inventive step because its protein-fat-fiber compositionsignificantly alters stabilizer hydration, drug solubilization, and freezing kineticscompared to dairy emulsions. Additionally, the present invention uniquely tailorspediatric drug-loading according to safe therapeutic limits while embedding theminto an ice-cream vehicle-a capability not taught, suggested, or enabled by anyprior work.Accordingly, the present invention overcomes multiple unresolved drawbacks ofearlier formulations by providing a non-dairy, vegan, allergen-conscious, noncariogenic, dual-drug compatible, pediatric analgesic ice-cream system withenhanced acceptability, improved safety, and simplified excipient architectureconstitutes a novel and non-obvious advancement that is disclosed by any existingprior art, thereby establishing a clear inventive step.3. Objective of the invention:The principal object of the present invention is to formulate a pharmaceutical icecream-type pediatric analgesic composition suitable for safe and effective oraladministration to children.Another object of the present invention is to formulate a vegan, dairy-free, noncariogenic sweetened frozen preparation incorporating pediatric analgesic agentssuch as ibuprofen and paracetamol.It is yet another object of the present invention to provide a process for preparingthe ice-cream-type pediatric analgesic formulation in a manner that ensuresuniform dispersion of the active pharmaceutical ingredients, desirable rheologicalbehaviour prior to freezing, and stable structural characteristics in the frozen state.It is a further object of the present invention to provide a pediatric-friendly,palatable dosage form that enhances acceptability, improves compliance, andreduces treatment-related discomfort, particularly during pediatric dentalprocedures.It is still another object of the present invention to formulate an ice-cream-typepediatric analgesic composition that exhibits acceptable physicochemicalproperties and biological safety suitable for pediatric use.4. Summary of the invention: To achieve the object, the present invention provides a pediatric analgesiccomposition in the form of an ice-cream-type pharmaceutical preparation designed toenhance oral acceptability, reduce treatment-related discomfort, and improvecompliance in pediatric subjects.According to the basic aspect, the invention offers a vegan, non-cariogenic frozenmatrix that serves as a suitable vehicle for delivering analgesic agents in a childfriendly and soothing manner.It is another aspect that the invention incorporates a plant-based milk system, a noncariogenic sweetening component, a stabilizing and gelling material, and at least onepediatric-appropriate analgesic, thereby forming a palatable frozen dosage form.It is one another aspect that the invention includes a method for preparing the icecream-type pharmaceutical composition through controlled mixing, stabilization,incorporation of the analgesic, and subsequent freezing to achieve the desiredconsistency.It is also another aspect that the formulation exhibits desirable sensory characteristics,stability attributes, and rheological behaviour suitable for pediatric administration.Finally, another aspect of the present invention is the provision of a method fordelivering analgesia to pediatric subjects, wherein the frozen composition providesboth pharmacological action and a cooling sensory effect that enhances treatmentacceptance, particularly during dental or orofacial procedures.5. Brief Description of the Drawings:The accompanying drawings are provided to enhance the understanding of the presentdisclosure and form an integral part of this specification. These figures illustratevarious aspects of the almond-milk-based pediatric analgesic ice-cream formulation,including its preparation, physicochemical characterization, and biologicalevaluation. The drawings further depict spectral, antimicrobial, kinetic, andcytotoxicity data that collectively support the formulation's stability, safety, andtherapeutic suitability for pediatric use. By incorporating these visual representations,the invention's technical components, preparation methods, and real-worldapplications are conveyed with greater clarity and comprehensiveness.Figure 1 illustrates the photographic representation of the four-almond milk-basedpediatric analgesic ice-cream formulations according to the present invention,depicting Group I (Paracetamol-loaded), Group II (Ibuprofen-loaded), Group III(combined Paracetamol + Ibuprofen), and Group IV (placebo almond-milk ice cream).Figure 2 illustrates the UV-Visible absorption spectra of the almond milk-basedpediatric analgesic ice-cream formulations according to the present invention,depicting the characteristic absorbance profiles according to the present invention.Figure 3 illustrates the antimicrobial activity of the almond milk-based pediatricanalgesic ice-cream formulations according to the present invention, showing the zonesof inhibition produced against the tested oral pathogenic microorganisms using the agarwell diffusion method according to the present invention.Figure 4A illustrates the time-kill kinetic curve of E. faecalis treated withformulationsaccording to the present inventionFigure 4B illustrates the time-kill kinetic curve of C. albicans treated with accordingto the present invention.Figure 4C illustrates the time-kill kinetic curve of S. aureus following exposure toformulations according to the present invention.Figure 4D illustrates the time-kill kinetic curve of Lactobacillus species treated withformulations according to the present invention.Figure 4E illustrates the time-kill kinetic curve of S. mutans exposed toformulations according to the present invention.Figure 5A illustrates the percentage inhibition of bovine serum albumindenaturation by the four formulations according to the present invention.Figure 5B illustrates the anti-inflammatory activity of Groups I-IV measured usingthe egg-albumin denaturation assay according to the present invention.Figure 5C illustrates the membrane-stabilizing activity of the formulationsaccording to the present invention.Figure 6 illustrates the Day 2 nauplii viability profile for Groups I-IV according tothe present invention.Figure 7 illustrates the ATR-FTIR spectra of Groups I-IV according to the presentinvention, showing characteristic peaks of ibuprofen, paracetamol, and the almondmilk matrix.Figure 8 illustrates representative microscopic images of zebrafish embryosexposed to Group I-IV formulations at Day 1, Day 2, and Day 3 according to thepresent invention.6. Detailed description of the Invention:The following is a detailed description of embodiments of the disclosure depicted inthe accompanying drawings. The embodiments are in such detail as to clearlycommunicate the disclosure. However, the amount of detail offered is not intended tolimit the anticipated variations of embodiments. On the contrary, the intention is tocover all modifications, equivalents, and alternatives falling within the spirit and scopeof the present disclosure as defined by the appended claims.Method 1: Preparation of Almond Milk-Based Analgesic Ice-CreamFormulationStep 1: Preparation of Almond Milk Ice-Cream FormulationAccording to one embodiment of the present invention, the formulation of the analgesicice-cream begins with the preparation of almond milk, which serves as the primarybase material. A total of 20 g of almonds were cleaned, blanched, and ground into afine powder using a laboratory grinder. The resulting almond powder was slowlyincorporated into 100 mL of distilled water under continuous stirring to ensure uniformdispersion of fat, protein, and fiber components. The mixture was allowed to hydratefor complete extraction of soluble constituents, thereby yielding fresh almond milk.The prepared almond milk was subsequently divided into four equal portions, eachtransferred into separate sterile glass beakers containing 25 mL of the almond milkbase. To each portion, 0.1 g of xanthan gum was added as a stabilizing and emulsifyingagent. The mixture was subjected to homogenization using a digital homogenizeroperated at 450 rpm for 2 hours, ensuring complete hydration of xanthan gum andachieving a smooth, semi-viscous consistency suitable for ice-cream base formation.Following the stabilization step, 0.5 g of xylitol was added to each beaker. Xylitol wasselected as a non-cariogenic sweetening agent, offering sweetness equivalent to sucrosewhile providing dental and metabolic advantages for pediatric applications. Themixture was again homogenized to allow complete dissolution and uniform distributionof the sweetener.Step 2: Preparation and Verification of Crude Ibuprofen and ParacetamolPowdersAccording to one embodiment, crude ibuprofen and paracetamol were prepared bymanually triturating the tablets, sieving the powders (60-mesh), and ensuring uniformparticle size for proper dispersion in the almond milk-based ice-cream formulations.Identity and purity were verified through preliminary checks-including characteristicodor, solubility, and melting point confirmation against pharmacopeial ranges(Ibuprofen 75-78 °C; Paracetamol 168-172 °C). Additional quality assessmentsincluded moisture analysis, visual inspection, and comprehensive characterization:ATR-FTIR, melting point, HPLC assay and related substances, Karl Fischer moisture,headspace GC for residual solvents, laser diffraction for particle size, microbial limits,and DSC / XRPD where required. Only batches meeting predefined acceptancestandards were used for formulation.Only after confirming that the crude powders met acceptable standards for identity,purity, and physical characteristics were the drugs incorporated into the almond-milkbase of the four formulation groups.This process ensured that the crude active ingredients were safe, compatible, anduniformly dispersible within the pediatric ice-cream formulation.The drug quantities incorporated into each formulation were selected based on standardpediatric dosing guidelines and accepted clinical recommendations for safe single-doseadministration. The amounts were calculated to ensure that each 50 mL serving of theanalgesic ice-cream fell within the therapeutically effective yet safe limits for pediatricuse.Step 3: Analgesic components incorporationAccording to one embodiment, the analgesic components were incorporated into thestabilized almond base depending on the formulation group:The pre-weighed quantities of each drug were added directly into the homogenizedbase and mixed thoroughly to ensure uniform dispersion. Homogenization assisted inimproving solubility, minimizing precipitation, and promoting even distribution of theactive drug throughout the matrix.The complete formulations were transferred into sterile, food-grade containers andplaced in a standard ice-cream freezer under controlled conditions (-18 °C to -20 °C).Freezing was continued until the mixtures attained the desired ice-cream consistency.Each formulation was then stored under frozen conditions until furtherphysicochemical, sensory, and biological evaluations were performed.Group I - Almond ice-cream base containing Ibuprofen 100mg per 50 ml (dosestandardized based on pediatric suitability).Group II -Almond ice-cream base containing Paracetamol 250 mg per 50 ml.Group III -Almond ice-cream base containing a combination of Paracetamol125 mg and Ibuprofen 100mg per 50 ml.Group IV -Plain almond ice-cream base without any active drug (control).The pre-weighed quantities of each drug were added directly into the homogenizedbase and mixed thoroughly to ensure uniform dispersion. Homogenization assisted inimproving solubility, minimizing precipitation, and promoting even distribution of theactive drug throughout the matrix.The complete formulations were transferred into sterile, food-grade containers andplaced in a standard ice-cream freezer under controlled conditions (-18 °C to -20 °C).Freezing was continued until the mixtures attained the desired ice-cream consistency.Each formulation was then stored under frozen conditions until furtherphysicochemical, sensory, and biological evaluations were performed. (Fig.1)Method 2: Physicochemical Characterization of the Almond Milk-BasedAnalgesic Ice-Cream FormulationAccording to one embodiment, the pH of each formulation-Ibuprofen (Group I),Paracetamol (Group II), Combination (Group III), and Control (Group IV)-wasmeasured at room temperature using a calibrated digital pH meter. Approximately 5 gof the pre-thawed sample was equilibrated before analysis, and all formulations showedpH values within the acceptable pediatric oral range. The viscosity of the formulationswas then assessed using a Brookfield viscometer at 20 and 50 rpm, and all samplesexhibited pseudoplastic flow typical of xanthan-stabilized frozen desserts, confirmingthat the xanthan concentration provided adequate structural integrity.Melting behaviour was evaluated by placing a 10 g scoop of each formulation on a preweighed glass plate at 28 ± 2 °C and recording the melting time. The use of xanthangum and homogenization at 450 rpm produced a uniform microstructure with slowermelting rates, with drug-loaded groups showing slightly enhanced melting stability.Overrun was determined gravimetrically by comparing the weights of equal volumesof mix (pre-freezing) and frozen ice cream, and all formulations achieved acceptableoverrun levels despite the absence of dairy fat, indicating effective air entrapment bythe almond-protein-stabilizer system.Sensory evaluation was carried out by trained reviewers who assessed appearance,colour, texture, taste, sweetness, and mouthfeel. Xylitol contributed smooth sweetnesswithout aftertaste, and homogenization ensured desirable texture, with drug-loadedformulations exhibiting no detectable bitterness due to adequate masking by thealmond base. Stability was assessed over 30 days at -18 °C, during which allformulations remained uniform with no phase separation, crystallization, pHfluctuations, or drug precipitation, demonstrating that the almond-xanthan matrixeffectively prevented ice-crystal growth and maintained the therapeutic distribution ofthe active ingredients.According to one embodiment of the present invention, UV-Visible spectroscopy wasused to confirm the presence and stability of ibuprofen and paracetamol within thealmond milk-based ice-cream formulations. Aqueous extracts of Groups I-IV wereprepared by thawing, diluting, and filtering through a 0.45 μm membrane.Spectral scans (200-400 nm) showed characteristic absorption peaks for Groups I andII near 360 nm, while Group III displayed a shifted peak around 300 nm. Group IVshowed only a mild absorbance near 355 nm, consistent with the drug-free almondmatrix. These profiles verified the presence of the active ingredients, with thecombination group exhibiting a matrix-related peak shift.Overall, the UV-Visible analysis confirmed drug stability, absence of degradation, andcompatibility of the active components with the almond-milk base. (Fig.2)Method 3: Evaluation of Antimicrobial Activity of the Almond Milk-Based IceCream Formulations (Agar Well Diffusion Method)According to one embodiment of the present invention, the antimicrobial activity offour almond milk-based ice-cream formulations (Group I-IV) was evaluated using theagar well diffusion method against selected oral pathogens. This technique was used todetermine inhibitory effects and compare antimicrobial potency among the groups.(Fig.3)Freeze-dried cultures were revived in appropriate broth media, incubated to activegrowth, and standardized to 0.5 McFarland (~1 x 108 CFU / mL). Sterile MHA and SDAplates were then inoculated with 100 μL of each standardized culture to create auniform lawn. Wells of 6 mm diameter were aseptically bored into the agar, and 50 μLof each formulation was added along with positive and vehicle controls, allowing platesto pre-diffuse for 30 minutes. Bacterial plates were incubated at 37 °C for 24 hours andfungal plates at 28-30 °C for 48 hours, with all tests performed in triplicate. Followingincubation, zones of inhibition were measured in millimetres using a digital Verniercaliper, and mean ± SD values were calculated. Average zone diameters showed thatGroup III produced the largest inhibition zones, followed by Group II and Group I,while Group IV (placebo) exhibited the smallest zones, consistent with the recordedexperimental data.According to one embodiment, the observed zones indicate that the almond milk-basedice-cream matrix permits diffusion of active agents and that paracetamol- andibuprofen-containing formulations display measurable antimicrobial effects in vitrounder agar diffusion conditions. The formulation demonstrated stronger inhibitionagainst C. albicans and E. faecalis, and moderate inhibition against S. mutans andLactobacillus spp. These findings support the concept that the ice-cream dosage formdoes not prevent drug diffusion and may impart adjunctive antimicrobial benefits inthe oral cavity when administered to pediatric patients.Method 4: Time-Kill Kinetic Analysis of the FormulationAccording to one embodiment of the present invention, a time-kill kinetic analysis wasperformed to evaluate antimicrobial interaction, microbial safety, and time-dependentmicrobial reduction of the four pediatric analgesic ice-cream formulations. Thismethod assessed whether the formulations inhibited, promoted, or remained neutraltoward microbial growth, ensuring suitability for pediatric oral use. The analysis wasconducted on all four groups. (Fig.4)a) Microbial Strains and Preparation of InoculumPediatric-relevant microorganisms (E. coli, S. aureus, P. aeruginosa) were grown onMHA at 37 °C for 18-20 hours. A standardized 0.5 McFarland inoculum (~1x108CFU / mL) was prepared. Cultures were pre-incubated for 4 hours in antimicrobialfree MHB to reach logarithmic phase.b) Assay Setup and Treatment ApplicationThirty microlitres of inoculum was added to 15 mL pre-warmed MHB, and 90 μLaliquots were dispensed into 96-well plates. Extracts of Groups I-IV were added toachieve final concentrations of 25, 50, and 100 μg / mL. Controls included untreatedbacteria (negative) and Amoxyrite (positive).c) Incubation and Kinetic MeasurementsPlates were incubated at 37 °C, and samples were collected at 0, 1, 2, 4, 6, and 24hours. Serial dilutions were plated on MHA to determine viable CFU / mL, generatingtime-kill curves for each group.Results were evaluated by comparing log10 reductions in CFU / mL relative to theuntreated control.- Group I (Ibuprofen formulation): Displayed mild bacteriostatic activity, consistentwith its known weak antimicrobial suppressive profile.- Group II (Paracetamol formulation): Demonstrated measurable bacteriostatic activitystronger than Group I, consistent with your recorded results showing greater timedependent reduction, likely due to better solubility and interaction with the microbialenvironment.- Group III (Ibuprofen + Paracetamol combination): Demonstrated the strongestbacteriostatic effect among all groups, showing the most rapid reduction in viablecount, attributable to additive physicochemical and stress-related mechanisms.- Group IV (placebo ice-cream base): Showed a neutral profile, with no significantbacterial proliferation or reduction, confirming that the excipients (xylitol, xanthangum, almond milk) do not support microbial overgrowth.None of the formulations exhibited bactericidal effects (>3 log10 reduction), aligningwith their pharmacological classification as analgesics rather than antimicrobials.The time-kill kinetic analysis confirms that all four groups are microbiologically safe,do not support the proliferation of common pediatric-relevant pathogens, and exhibitstable microbial interaction profiles suitable for an ingestible pediatric frozen dosageform. The results validate that the formulation matrix maintains microbial neutralityeven under simulated contamination exposure, supporting its safe use, handling, andshort-term storage.Method 5: Evaluation of Anti-inflammatory ActivityAccording to one embodiment of the present invention, the anti-inflammatory potentialof the four pediatric ice cream-type formulations was evaluated using three in vitromodels: BSA denaturation, egg-albumin denaturation, and HRBC membranestabilization. These assays simulate protein denaturation and membrane lysis. Extractsof Groups I (Ibuprofen), II (Paracetamol), III (Ibuprofen + Paracetamol), and IV(placebo) were tested at 10-50 μg / mL. (Fig.5)In the BSA assay, mixtures were incubated and heated before measuring absorbance at660 nm. All groups showed dose-dependent inhibition, with Group I exhibiting thehighest activity, followed closely by Group III, while Group II showed moderate andGroup IV minimal inhibition.The egg-albumin assay produced similar results: Group I showed the greatestprotection, Group III followed closely, Group II showed moderate inhibition, andGroup IV minimal effect.For the membrane stabilization assay, treated RBC suspensions were incubated andanalyzed for hemoglobin release. All groups demonstrated membrane-stabilizingeffects, with Group I again highest, followed by Group III, then Group II, and minimalstabilization in Group IV.Overall, the formulations demonstrated measurable anti-inflammatory activity,particularly Groups I and III. The results confirm that the active ingredients retainbioactivity within the frozen matrix and that the excipients do not induce proteindenaturation or membrane damage, supporting the safety and biocompatibility of thepediatric formulations.Method 6: Cytotoxicity Evaluation of the FormulationAccording to one embodiment of the present invention, the cytotoxic potential of thepediatric analgesic ice cream-type formulations was assessed using the brine shrimp(Artemia salina) lethality assay, a standard preliminary toxicity test that evaluatesnauplii mortality across different concentrations. (Fig.6)Brine shrimp cysts were hatched in artificial seawater under aeration and illumination,and active second-instar nauplii were exposed to formulation extracts at 5, 10, 20, 40,and 80 μg / mL. Ten nauplii were placed in 5 mL of each test solution, with artificialseawater as the negative control. All treatments were performed in triplicate andincubated for 24 hours, after which survival was recorded and percentage mortalitycalculated.Groups I and II showed 100% survival at all concentrations, indicating excellentbiocompatibility. Group III maintained >90% viability even at 80 μg / mL,demonstrating minimal cytotoxicity. Group IV showed a slight reduction in viability athigher concentrations.Overall, all formulations fell within accepted non-toxic limits for the brine shrimpassay (LC50 > 100 μg / mL), confirming that the pediatric analgesic ice cream-typeformulations are safe, biocompatible, and suitable for further biological evaluation.Method 7: FTIR Characterisation of the FormulationAccording to one embodiment of the present invention, the structural integrity andfunctional group characteristics of the pediatric analgesic ice cream-typeformulations were evaluated using FTIR spectroscopy to assess drug-excipientcompatibility through characteristic peak analysis. (Fig.7)Formulations from Groups I-IV (Ibuprofen, Paracetamol, Combination, andPlacebo) were analysed using ATR-FTIR in the 4000-400 cm-1 range. Sampleswere placed directly on the ATR crystal, and spectra were recorded at 4 cm-1resolution with 32 scans before comparison with reference standards.Group I showed ibuprofen-specific peaks-ester C=O (~1735-1745 cm-1),aliphatic C-H (2920-2850 cm-1), and aromatic C=C (1600-1640 cm-1)-withoutshifting, confirming structural stability. Group II displayed characteristicparacetamol peaks, including O-H / N-H stretching (3280-3320 cm-1), aromaticvibrations (1600-1620 cm-1), and amide II (~1540-1550 cm-1).Group III exhibited superimposed peaks of both drugs without displacement,indicating no chemical interaction or degradation. Group IV presented onlyalmond-milk-related peaks, such as broad O-H, aliphatic C-H, and polysaccharideC-O (~1030-1040 cm-1).Overall, FTIR analysis confirmed well-preserved drug signatures and absence ofpeak shifts, validating the chemical stability and compatibility of ibuprofen,paracetamol, and their combination within the almond-milk ice cream matrix.Method 8: Embryotoxicity Assessment Using Zebrafish ModelAccording to one embodiment of the present invention, the embryotoxicity anddevelopmental safety of the four pediatric analgesic ice cream-type formulations wereevaluated using the zebrafish (Danio rerio) embryo model, a widely accepted in vivoscreening system for assessing the potential developmental toxicity of pharmaceuticaland nutraceutical formulations. (Fig.8)Adult wild-type zebrafish were maintained under controlled conditions (28 ± 2 °C,14:10 h light-dark cycle, pH 6.8-8.5) and fed twice daily. Fertilized embryos wereobtained through natural spawning, rinsed with E3 medium, and only healthy embryoswere selected.To assess embryotoxicity, aqueous extracts of Groups I-IV (Ibuprofen, Paracetamol,Combination, Placebo) were prepared at 5-80 μg / mL. Twenty embryos were placed in2 mL of each treatment per well, in triplicate. Extracts were dispersed in E3 medium,sonicated, and maintained at pH 7.2-7.3. Plates were kept at 28 °C and protected fromlight.Embryos were monitored up to 96 hpf, with observations at 24, 48, 72, and 96 h.Controls were maintained in E3 medium. Mortality, hatching, and developmentalabnormalities were evaluated following standard guidelines.Embryos showed normal survival and hatching up to 20 μg / mL. At 40 μg / mL, GroupsI and II maintained 100% hatching, while Groups III and IV showed a mild reduction(80%). At 80 μg / mL, Group IV exhibited the greatest reduction, whereas Groups I-IIIretained acceptable viability. No significant malformations were observed, and allgroups remained comparable to controls.These findings confirm that the pediatric analgesic ice-cream formulations are nonembryotoxic, biocompatible, and safe for developmental exposure, with no evidenceof teratogenic effects at the tested concentrations.The primary advantage of this invention lies in introducing an ice cream-typepediatric analgesic formulation, an unexplored approach to delivering analgesicdrugs through a vegan, non-cariogenic, xylitol-sweetened frozen base. Byintegrating dairy-free components with established pediatric analgesics, theinvention broadens the application of frozen dosage forms and provides a novel,palatable, and child-friendly drug delivery system that enhances acceptability,cooperation, and comfort. This formulation improves drug compliance by pairingtherapeutic analgesic effects with a pleasant sensory experience, offering a superioralternative to conventional syrups or tablets with fewer acceptance challenges andadded behavioral benefits during dental procedures. It enables controlled release,reduces procedural stress through its cooling effect, and supports effective painmanagement, making it well suited for clinical and community pediatric care.Overall, this vegan almond-milk-based, non-cariogenic formulation represents aninventive advancement in pediatric analgesic delivery by improving palatability,safety, and cooperation in young patients.TABLEIngredient Quantity

Claims

1. A pediatric analgesic ice-cream-type pharmaceutical composition comprising: a plant-based milk base; a non-cariogenic sweetener; a stabilizing and gelling agent; and at least one analgesic selected from ibuprofen, paracetamol, or a combination thereof; wherein the plant-based milk base comprises almond milk; wherein the non-cariogenic sweetener comprises a sugar alcohol; wherein the stabilizing and gelling agent comprises a polysaccharide gum; and wherein the composition is frozen to obtain an ice-cream-type pediatric dosage form suitable for oral administration.

2. A method for preparing the pediatric analgesic ice-cream-type composition as claimed in claim 1, the method comprising: preparing an almond-milk base by mixing almond powder with distilled water; dividing the almond-milk base into predetermined portions; adding a gelling agent comprising xanthan gum to each portion and homogenizing to obtain a uniform stabilized mixture; adding a non-cariogenic sweetener comprising xylitol and further homogenizing to ensure uniform dispersion; incorporating an analgesic selected from ibuprofen, paracetamol, or a combination thereof into the homogenized mixture; and freezing the mixture at a temperature sufficient to obtain an ice-cream-type pediatric dosage form suitable for oral administration.

3. The method of claim 2, wherein the almond-milk base is prepared by mixing 20 g of almond powder with 100 mL of distilled water; wherein xanthan gum is added in an amount of 0.1 g per portion; wherein xylitol is added in an amount of 0.5 g per portion; and wherein freezing is carried out between -18°C and -20°C.

4. The pediatric analgesic composition as claimed in claim 1, wherein the pH of the formulation is adjusted within a range of 6.0 to 7.5 to provide pediatric oral acceptability.

5. The pediatric analgesic composition as claimed in claim 1, wherein the prefrozen mixture exhibits non-Newtonian pseudoplastic flow behaviour.

6. The pediatric analgesic composition as claimed in claim 1, wherein the frozen formulation exhibits melting stability characterized by a reduced melting rate, absence of phase separation, and uniform distribution of the incorporated analgesic, the said melting stability being attributable to homogenization of the formulation and the presence of a polysaccharide gelling agent comprising xanthan gum.

7. The pediatric analgesic composition as claimed in claim 1, wherein the formulation exhibits antimicrobial activity against Enterococcus faecalis, Staphylococcus aureus, Candida albicans, Lactobacillus spp., and Streptococcus mutans.

8. The pediatric analgesic composition as claimed in claim 1, wherein the formulation exhibits anti-inflammatory activity attributable to the incorporated analgesic agent or combination thereof.

9. The pediatric analgesic composition as claimed in any of the preceding claims, wherein the formulation remains physically and chemically stable during frozen storage, without drug precipitation, syneresis, or formation of ice crystals.

10. The pediatric analgesic ice-cream-type composition as claimed in claim 1, for use in enhancing pediatric analgesic administration by providing a cooling effect that improves comfort and cooperation during dental procedures.